PNAS Nexus最新文献_第2页

DAPK3 modulates migration and invasion of triple negative breast cancer cells DAPK3 可调节三阴性乳腺癌细胞的迁移和侵袭

PNAS Nexus Pub Date : 2024-09-13 DOI: 10.1093/pnasnexus/pgae401

Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H-F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis

{"title":"DAPK3 modulates migration and invasion of triple negative breast cancer cells","authors":"Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H-F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis","doi":"10.1093/pnasnexus/pgae401","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae401","url":null,"abstract":"Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) leading to the observation that Death-Associated Protein Kinase 3 (DAPK3) is significantly and specifically overexpressed in the triple negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, in both TNBC cell lines and tumors, independent of mRNA levels. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with downregulation of an epithelial-mesenchymal transition (EMT) signature, which was confirmed in vivo. The kinase and leucine-zipper domains within DAPK3 were shown by mutational analysis to be essential for functionality. Notably, DAPK3 was found to inhibit the levels of desmoplakin (DSP), a crucial component of the desmosome complex, thereby explaining the observed migration and invasion effects. Further exploration with immunoprecipitation-mass spectrometry (IP-MS) identified that Leucine-Zipper Protein 1 (LUZP1) is a preferential binding partner of DAPK3. LUZP1 engages in a leucine-zipper-domain-mediated interaction that protects DAPK3 from proteasomal degradation. Thus, the DAPK3/LUZP1 heterodimer emerges as a novel regulator of EMT/desmosome components that promote TNBC cell migration.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Groundwater sustainability in India through non-rice dominated cropping pattern 印度通过非水稻为主的种植模式实现地下水的可持续性

PNAS Nexus Pub Date : 2024-09-11 DOI: 10.1093/pnasnexus/pgae378

Swarup Dangar, Vimal Mishra

{"title":"Groundwater sustainability in India through non-rice dominated cropping pattern","authors":"Swarup Dangar, Vimal Mishra","doi":"10.1093/pnasnexus/pgae378","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae378","url":null,"abstract":"Over-exploitation of groundwater for irrigation caused a rapid groundwater depletion in north India, leading to food and water security challenges. However, the crucial role of changing cropping patterns on groundwater savings under the observed and projected warming climate remains unexplored. Here, we show that altering the existing rice dominated cropping systems in India can be a potential solution for groundwater sustainability under the current and future climate. Satellite and model-based estimates show that north India lost ∼336 and 297 km3 of groundwater, respectively during 2002-2022. We developed optimized crop switching scenarios for groundwater savings considering nutritional requirements, farmers’ profit, and crop production. Crop switching considering all the three targets (crop switch one: CSI) and allowing rice replacement with alternate crops (crop switch two: CSII) could save 45 and 91 km3 groundwater, respectively in north India during the observed climate (2002-2022) compared to the current cropping pattern. Altering the current cropping pattern can lead to substantial groundwater savings under the projected future climate without comprising nutritional targets and farmers’ profit at the state level. Replacing 37% area of rice with other crops (CSII) can recover 61 to108 km3 groundwater compared to -13 to 43 km3 with current cropping pattern under the 1.5-3°C global warming levels. Similarly, under the CSI scenario, 36 to 86 km3 groundwater can be recovered in the future warming world. Moreover, the benefits of crop switching in groundwater saving are higher during the prolonged dry periods compared to the baseline under the warming climate. Therefore, crop switching offers substantial benefits for groundwater sustainability under the current and projected future climate in India.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CYP7B1 deficiency impairs myeloid cell activation in autoimmune disease of the central nervous system CYP7B1 缺乏症会影响中枢神经系统自身免疫性疾病中髓细胞的活化

PNAS Nexus Pub Date : 2024-09-11 DOI: 10.1093/pnasnexus/pgae334

Huanhuan Song, Aowei Lv, Zhibao Zhu, Runyun Li, Qiuping Zhao, Xintong Yu, Junyi Jiang, Xiang Lin, Cunjin Zhang, Rui Li, Yaping Yan, Wanjin Chen, Ning Wang, Ying Fu

{"title":"CYP7B1 deficiency impairs myeloid cell activation in autoimmune disease of the central nervous system","authors":"Huanhuan Song, Aowei Lv, Zhibao Zhu, Runyun Li, Qiuping Zhao, Xintong Yu, Junyi Jiang, Xiang Lin, Cunjin Zhang, Rui Li, Yaping Yan, Wanjin Chen, Ning Wang, Ying Fu","doi":"10.1093/pnasnexus/pgae334","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae334","url":null,"abstract":"Dysregulation of cholesterol metabolism underlies neurodegenerative disease and is increasingly implicated in neuroinflammatory diseases, such as multiple sclerosis (MS). Cytochrome P450 family 7 subfamily B member 1 (CYP7B1) is a key enzyme in alternative cholesterol metabolism. A recessive mutation in the gene CYP7B1 is known to cause a neurodegenerative disease, hereditary spastic paraplegia type 5 and oxysterol accumulation. However, the role of CYP7B1 in neuroinflammation has been little revealed. In this study, we induced experimental autoimmune encephalomyelitis (EAE), as a murine model of MS, using CYP7B1 homozygous knockout (KO) mice. We found that CYP7B1 deficiency can significantly attenuate EAE severity. CYP7B1 deficiency is sufficient to reduce leukocyte infiltration into the central nervous system, suppress proliferation of pathogenic CD4+ T cells, and decrease myeloid cell activation during EAE. Additionally, live-animal imaging targeting translocator protein expression, an outer mitochondrial membrane protein biomarker of neuroinflammation, showed that CYP7B1 deficiency results in suppressed neuroinflammation. Using human monocyte-derived microglia-like cellular disease model and primary microglia of CYP7B1 KO mice, we also found that activation of microglia of CYP7B1 deficiency was impaired. These cumulative results suggest that CYP7B1 can regulate neuroinflammation, thus providing potential new targets for therapeutic intervention.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chirality and odd mechanics in active columnar phases 活性柱状相中的手性和奇异力学

PNAS Nexus Pub Date : 2024-09-10 DOI: 10.1093/pnasnexus/pgae398

S J Kole, Gareth P Alexander, Ananyo Maitra, Sriram Ramaswamy

引用次数: 0

Simulating cardiac fluid dynamics in the human heart 模拟人体心脏的心肌流体动力学

PNAS Nexus Pub Date : 2024-09-10 DOI: 10.1093/pnasnexus/pgae392

Marshall Davey, Charles Puelz, Simone Rossi, Margaret Anne Smith, David R Wells, Gregory M Sturgeon, William Paul Segars, John P Vavalle, Charles S Peskin, Boyce E Griffith

{"title":"Simulating cardiac fluid dynamics in the human heart","authors":"Marshall Davey, Charles Puelz, Simone Rossi, Margaret Anne Smith, David R Wells, Gregory M Sturgeon, William Paul Segars, John P Vavalle, Charles S Peskin, Boyce E Griffith","doi":"10.1093/pnasnexus/pgae392","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae392","url":null,"abstract":"Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions. However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the valves are limited in their abilities to predict valve performance, capture fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac fluid-structure interaction (FSI) in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first FSI model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and that its responses to changes in loading conditions are consistent with the Frank-Starling mechanism. These complex relationships emerge intrinsically from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical interventions. They also can provide platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Measuring receptivity to misinformation at scale on a social media platform 大规模衡量社交媒体平台对错误信息的接受程度

PNAS Nexus Pub Date : 2024-09-10 DOI: 10.1093/pnasnexus/pgae396

Christopher K Tokita, Kevin Aslett, William P Godel, Zeve Sanderson, Joshua A Tucker, Jonathan Nagler, Nathaniel Persily, Richard Bonneau

{"title":"Measuring receptivity to misinformation at scale on a social media platform","authors":"Christopher K Tokita, Kevin Aslett, William P Godel, Zeve Sanderson, Joshua A Tucker, Jonathan Nagler, Nathaniel Persily, Richard Bonneau","doi":"10.1093/pnasnexus/pgae396","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae396","url":null,"abstract":"Measuring the impact of online misinformation is challenging. Traditional measures, such as user views or shares on social media, are incomplete because not everyone who is exposed to misinformation is equally likely to believe it. To address this issue, we developed a method that combines survey data with observational Twitter data to probabilistically estimate the number of users both exposed to and likely to believe a specific news story. As a proof of concept, we applied this method to 139 viral news articles and find that although false news reaches an audience with diverse political views, users who are both exposed and receptive to believing false news tend to have more extreme ideologies. These receptive users are also more likely to encounter misinformation earlier than those who are unlikely to believe it. This mismatch between overall user exposure and receptive user exposure underscores the limitation of relying solely on exposure or interaction data to measure the impact of misinformation, as well as the challenge of implementing effective interventions. To demonstrate how our approach can address this challenge, we then conducted data-driven simulations of common interventions used by social media platforms. We find that these interventions are only modestly effective at reducing exposure among users likely to believe misinformation, and their effectiveness quickly diminishes unless implemented soon after misinformation's initial spread. Our paper provides a more precise estimate of misinformation's impact by focusing on the exposure of users likely to believe it, offering insights for effective mitigation strategies on social media.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soft cells and the geometry of seashells 软细胞和贝壳的几何形状

PNAS Nexus Pub Date : 2024-09-10 DOI: 10.1093/pnasnexus/pgae311

Gábor Domokos, Alain Goriely, Ákos G Horváth, Krisztina Regős

引用次数: 0

The lysogenic filamentous Pseudomonas bacteriophage phage Pf slows mucociliary transport 溶解性丝状假单胞菌噬菌体噬菌体 Pf 可减缓粘膜运输速度

PNAS Nexus Pub Date : 2024-09-09 DOI: 10.1093/pnasnexus/pgae390

Elizabeth B Burgener, Pamela Cai, Michael J Kratochvil, Laura S Rojas-Hernandez, Nam Soo Joo, Aditi Gupta, Patrick R Secor, Sarah C Heilshorn, Andrew J Spakowitz, Jeffrey J Wine, Paul L Bollyky, Carlos E Milla

{"title":"The lysogenic filamentous Pseudomonas bacteriophage phage Pf slows mucociliary transport","authors":"Elizabeth B Burgener, Pamela Cai, Michael J Kratochvil, Laura S Rojas-Hernandez, Nam Soo Joo, Aditi Gupta, Patrick R Secor, Sarah C Heilshorn, Andrew J Spakowitz, Jeffrey J Wine, Paul L Bollyky, Carlos E Milla","doi":"10.1093/pnasnexus/pgae390","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae390","url":null,"abstract":"Pseudomonas aeruginosa is a major pulmonary pathogen causing chronic pulmonary infections in people with Cystic Fibrosis (CF). The P. aeruginosa filamentous and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms. Liquid crystalline biofilms are more adherent and viscous than those with out liquid crystals. A key feature of biofilms to enhance bacterial adherence and resist physicial clearance. The effect of Pf phage on mucociliary transport is unknown. We found that primary CF and non-CF nasal epithelial cells cultured at air liquid interface treated with Pf phage exhibit liquid crystalline structures in the overlying mucus. On these cell cultures, Pf phage entangles cilia but does not affect ciliary beat frequency. In both these in vitro cell cultures and in an ex vivo porcine trachea model introduction of Pf phage decreases mucociliary transport velocity. Pf phage also blocks the rescue of mucociliary transport by cystic fibrosis transmembrane conductance regulator modulators in CF cultures. Thus, Pf phage may contribute to the pathogenesis of P. aeruginosa-associated CF lung disease via induction of liquid crystalline characteristics to airway secretions, leading to impaired mucociliary transport. Targeting Pf phage may be useful in treatment CF as well as other settings of chronic P. aeruginosa infections.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stealthy and hyperuniform isotropic photonic bandgap structure in 3D 三维隐形超均匀各向同性光子带隙结构

PNAS Nexus Pub Date : 2024-09-07 DOI: 10.1093/pnasnexus/pgae383

Lukas Siedentop, Gianluc Lui, Georg Maret, Paul M Chaikin, Paul J Steinhardt, Salvatore Torquato, Peter Keim, Marian Florescu

{"title":"Stealthy and hyperuniform isotropic photonic bandgap structure in 3D","authors":"Lukas Siedentop, Gianluc Lui, Georg Maret, Paul M Chaikin, Paul J Steinhardt, Salvatore Torquato, Peter Keim, Marian Florescu","doi":"10.1093/pnasnexus/pgae383","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae383","url":null,"abstract":"In photonic crystals the propagation of light is governed by their photonic band structure, an ensemble of propagating states grouped into bands, separated by photonic band gaps. Due to discrete symmetries in spatially strictly periodic dielectric structures their photonic band structure is intrinsically anisotropic. However, for many applications, such as manufacturing artificial structural color materials or developing photonic computing devices, but also for the fundamental understanding of light-matter interactions, it is of major interest to seek materials with long range non-periodic dielectric structures which allow the formation of isotropic photonic band gaps. Here, we report the first ever 3D isotropic photonic band gap for an optimized disordered stealthy hyperuniform structure for microwaves. The transmission spectra are directly compared to a diamond pattern and an amorphous structure with similar node density. The band structure is measured experimentally for all three microwave structures, manufactured by 3D-Laser-printing for meta-materials with refractive index up to ɳ =2.1. Results agree well with finite-difference-time-domain numerical investigations and a priori calculations of the band-gap for the hyperuniform structure: the diamond structure shows gaps but being anisotropic as expected, the stealthy hyperuniform pattern shows an isotropic gap of very similar magnitude, while the amorphous structure does not show a gap at all. Since they are more easily manufactured, prototyping centimeter scaled microwave structures may help optimizing structures in the technologically very interesting region of infrared (IR).","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid aqueous-phase dark reaction of phenols with nitrosonium ions: Novel mechanism for atmospheric nitrosation and nitration at low pH 苯酚与亚硝基鏻离子的快速水相暗反应：低 pH 条件下大气亚硝酸化和硝化的新机制

PNAS Nexus Pub Date : 2024-09-06 DOI: 10.1093/pnasnexus/pgae385

Baohua Cai, Yixiang Wang, Xin Yang, Yanchen Li, Jinghao Zhai, Yaling Zeng, Jianhuai Ye, Lei Zhu, Tzung-May Fu, Qi Zhang

{"title":"Rapid aqueous-phase dark reaction of phenols with nitrosonium ions: Novel mechanism for atmospheric nitrosation and nitration at low pH","authors":"Baohua Cai, Yixiang Wang, Xin Yang, Yanchen Li, Jinghao Zhai, Yaling Zeng, Jianhuai Ye, Lei Zhu, Tzung-May Fu, Qi Zhang","doi":"10.1093/pnasnexus/pgae385","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae385","url":null,"abstract":"Dark aqueous-phase reactions involving the nitrosation and nitration of aromatic organic compounds play a significant role in the production of light-absorbing organic carbon in the atmosphere. This process constitutes a crucial aspect of tropospheric chemistry and has attracted growing research interest, particularly in understanding the mechanisms governing nighttime reactions between phenols and nitrogen oxides. In this study, we present new findings concerning the rapid dark reactions between phenols containing electron-donating groups and inorganic nitrite in acidic aqueous solutions with pH levels below 3.5. This reaction generates a substantial amount of nitroso- and nitro-substituted phenolic compounds, known for their light-absorbing properties and toxicity. In experiments utilizing various substituted phenols, we demonstrate that their reaction rates with nitrite depend on the electron cloud density of the benzene ring, indicative of an electrophilic substitution reaction mechanism. Control experiments and theoretical calculations indicate that the nitrosonium ion (NO+) is the reactive nitrogen species responsible for undergoing electrophilic reactions with phenolate anions, leading to the formation of nitroso-substituted phenolic compounds. These compounds then undergo partial oxidation to form nitro-substituted phenols through reactions with nitrous acid (HONO) or other oxidants like oxygen. Our findings unveil a novel mechanism for swift atmospheric nitrosation and nitration reactions that occur within acidic cloud droplets or aerosol water, providing valuable insights into the rapid nocturnal formation of nitrogen-containing organic compounds with significant implications for climate dynamics and human health.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0