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Accredited ocean sanctuaries for transforming captive cetacean care. 认可的海洋保护区,以改变圈养鲸类的护理。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003166
Lori Marino, Charles Vinick, Katy Foster, Jeff Foster, Rob Hicks, Graham McGrath, John Racanelli, Janesse Brewer
{"title":"Accredited ocean sanctuaries for transforming captive cetacean care.","authors":"Lori Marino, Charles Vinick, Katy Foster, Jeff Foster, Rob Hicks, Graham McGrath, John Racanelli, Janesse Brewer","doi":"10.1371/journal.pbio.3003166","DOIUrl":"10.1371/journal.pbio.3003166","url":null,"abstract":"<p><p>Increasing concerns over the welfare of captive cetaceans (dolphins, whales, and porpoises) have led to calls for their transfer from marine parks and aquariums to sanctuaries. We describe an unprecedented collaboration to develop the first accreditation guidelines for authentic ocean sanctuaries to transform cetacean care.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003166"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice. 从团聚核到内侧前额皮质的兴奋性投射调节小鼠的疼痛和抑郁样行为。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003170
Shu-Ting Bao, Fang Rao, Cui Yin, Yong Niu, Jun-Li Cao, Cheng Xiao, Chunyi Zhou
{"title":"Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice.","authors":"Shu-Ting Bao, Fang Rao, Cui Yin, Yong Niu, Jun-Li Cao, Cheng Xiao, Chunyi Zhou","doi":"10.1371/journal.pbio.3003170","DOIUrl":"10.1371/journal.pbio.3003170","url":null,"abstract":"<p><p>The medial prefrontal cortex (mPFC) is implicated in emotional processing, cognition, and pain sensation, moreover, its circuitry undergoes neuroplastic changes in chronic pain. Although the nucleus reuniens (RE) of the thalamus provides significant glutamatergic inputs to the mPFC, it remains unclear whether this projection contributes to plasticity changes in the mPFC and pain-related behaviors in chronic pain. Using fiber photometry, we demonstrated that RE neurons responded to pain stimulation and emotional changes. Optogenetic activation of RE neurons and their projections to the mPFC (RE-mPFC projection) elicits hyperalgesia and depression-like behaviors in naïve mice. In a neuropathic pain mouse model, RE neurons were hyperactive, and the RE-mPFC projection was enhanced with a marked preference for the part innervating GABAergic circuits in the mPFC to that controlling mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Expectedly, optogenetic inhibition of RE neurons and the RE-mPFC projection ameliorated pain-like and depression-like behaviors in neuropathic pain mice. Additionally, chemogenetic inhibition of RE-mPFC neurons conferred analgesia in neuropathic pain mice exposed to both acute and chronic morphine. Our findings highlight the significant role of the RE-mPFC pathway in neuropathic pain comorbid with depression, suggesting its potential as a target for treatment of neuropathic pain.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003170"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth. 生物相关膜的渗透性选择与地球上生命的立体化学相匹配。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003155
Olivia Goode, Urszula Łapińska, Juliano Morimoto, Georgina Glover, David S Milner, Alyson E Santoro, Stefano Pagliara, Thomas A Richards
{"title":"Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth.","authors":"Olivia Goode, Urszula Łapińska, Juliano Morimoto, Georgina Glover, David S Milner, Alyson E Santoro, Stefano Pagliara, Thomas A Richards","doi":"10.1371/journal.pbio.3003155","DOIUrl":"10.1371/journal.pbio.3003155","url":null,"abstract":"<p><p>Early in the evolution of life, a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not. One key feature of known life is the utilization of right-handed d-ribose and d-deoxyribose sugars and left-handed l-amino acid stereochemical isomers (enantiomers); however, it is not clear why life adopted this specific chirality. Generally, archaea have l-phospholipid membrane chemistries and bacteria and eukaryotes have d-phospholipid membrane chemistries. We previously demonstrated that an l-archaeal and a d-intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a 'hybrid' membrane), displayed increased permeability for several key compounds compared to bacterial-like membranes. Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars, and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for d-ribose and d-deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of l-amino acids. This repertoire includes alanine, the plausible first l-amino acid utilized. We conclude such compartments could provide stereochemical compound selection matching those used by the core metabolism of life.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003155"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Object knowledge representation in the human visual cortex requires a connection with the language system. 人类视觉皮层中的对象知识表征需要与语言系统相连接。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003161
Bo Liu, Xiaosha Wang, Xiaoying Wang, Yan Li, Yang Han, Jiahui Lu, Hui Zhang, Xiaochun Wang, Yanchao Bi
{"title":"Object knowledge representation in the human visual cortex requires a connection with the language system.","authors":"Bo Liu, Xiaosha Wang, Xiaoying Wang, Yan Li, Yang Han, Jiahui Lu, Hui Zhang, Xiaochun Wang, Yanchao Bi","doi":"10.1371/journal.pbio.3003161","DOIUrl":"10.1371/journal.pbio.3003161","url":null,"abstract":"<p><p>How world knowledge is stored in the human brain is a central question in cognitive neuroscience. Object knowledge effects have been commonly observed in higher-order sensory association cortices, with the role of language being highly debated. Using object color as a test case, we investigated whether communication with the language system plays a necessary role in knowledge neural representation in the visual cortex and corresponding behaviors, combining diffusion imaging (measuring white-matter structural integrity), functional MRI (fMRI; measuring functional neural representation of knowledge), and neuropsychological assessments (measuring behavioral integrity) in a group of patients who suffered from stroke (N = 33; 18 with left-hemisphere lesions, 11 with right-hemisphere lesions, and 4 with bilateral lesions). The structural integrity loss of the white-matter connection between the anterior temporal language region and the ventral visual cortex had a significant effect on the neural representation strength of object color knowledge in the ventral visual cortex and on object color knowledge behavior across modalities. These contributions could not be explained by the potential effects of the early visual perception pathway or potential confounding brain or cognitive variables. Our experiments reveal the contribution of the vision-language connection in the ventral occipitotemporal cortex (VOTC) object knowledge neural representation and object knowledge behaviors, highlighting the significance of the language-sensory system interface.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003161"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rewarding animals based on their subjective percepts is enabled by online Bayesian estimation of perceptual biases. 基于动物主观感知的奖励是通过在线贝叶斯感知偏差估计实现的。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-20 DOI: 10.1371/journal.pbio.3002764
Yelin Dong, Gabor Lengyel, Sabyasachi Shivkumar, Akiyuki Anzai, Grace F DiRisio, Ralf M Haefner, Gregory C DeAngelis
{"title":"Rewarding animals based on their subjective percepts is enabled by online Bayesian estimation of perceptual biases.","authors":"Yelin Dong, Gabor Lengyel, Sabyasachi Shivkumar, Akiyuki Anzai, Grace F DiRisio, Ralf M Haefner, Gregory C DeAngelis","doi":"10.1371/journal.pbio.3002764","DOIUrl":"10.1371/journal.pbio.3002764","url":null,"abstract":"<p><p>Elucidating the neural basis of perceptual biases, such as those produced by visual illusions, can provide powerful insights into the neural mechanisms of perceptual inference. However, studying the subjective percepts of animals poses a fundamental challenge: unlike human participants, animals cannot be verbally instructed to report what they see, hear, or feel. Instead, they must be trained to perform a task for reward, and researchers must infer from their responses what the animal perceived. However, animals' responses are shaped by reward feedback, thus raising the major concern that the reward regimen may alter the animal's decision strategy or even their intrinsic perceptual biases. Using simulations of a reinforcement learning agent, we demonstrate that conventional reward strategies fail to allow accurate estimation of perceptual biases. We developed a method that estimates perceptual bias during task performance and then computes the reward for each trial based on the evolving estimate of the animal's perceptual bias. Our approach makes use of multiple stimulus contexts to dissociate perceptual biases from decision-related biases. Starting with an informative prior, our Bayesian method updates a posterior over the perceptual bias after each trial. The prior can be specified based on data from past sessions, thus reducing the variability of the online estimate and allowing it to converge to a stable value over a small number of trials. After validating our method on synthetic data, we apply it to estimate perceptual biases of monkeys in a motion direction discrimination task in which varying background optic flow induces robust perceptual biases. This method overcomes an important challenge to understanding the neural basis of subjective percepts.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3002764"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei operates also in the gluconeogenic direction. 布鲁氏锥虫的糖体atp依赖性磷酸果糖激酶也在糖异生方向起作用。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-16 DOI: 10.1371/journal.pbio.3002938
Nicolas Plazolles, Hanna Kulyk, Edern Cahoreau, Marc Biran, Marion Wargnies, Erika Pineda, Mohammad El Kadri, Aline Rimoldi, Perrine Hervé, Corinne Asencio, Loïc Rivière, Paul A M Michels, Daniel Inaoka, Emmanuel Tétaud, Jean-Charles Portais, Frédéric Bringaud
{"title":"The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei operates also in the gluconeogenic direction.","authors":"Nicolas Plazolles, Hanna Kulyk, Edern Cahoreau, Marc Biran, Marion Wargnies, Erika Pineda, Mohammad El Kadri, Aline Rimoldi, Perrine Hervé, Corinne Asencio, Loïc Rivière, Paul A M Michels, Daniel Inaoka, Emmanuel Tétaud, Jean-Charles Portais, Frédéric Bringaud","doi":"10.1371/journal.pbio.3002938","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002938","url":null,"abstract":"<p><p>In the glucose-free environment of the midgut of the tsetse fly vector, the procyclic forms of Trypanosoma brucei primarily consume proline to feed its central carbon and energy metabolism. In this context, the parasite produces through gluconeogenesis, glucose 6-phosphate (G6P), the precursor of essential metabolic pathways, from proline catabolism. We show here that the parasite uses three different enzymes to perform the key gluconeogenic reaction producing fructose 6-phosphate (F6P) from fructose 1,6-bisphosphate, (i) fructose-1,6-bisphosphatase (FBPase), the canonical enzyme performing this reaction, (ii) sedoheptulose-1,7-bisphosphatase (SBPase), and (iii) more surprisingly ATP-dependent phosphofructokinase (PFK), an enzyme considered to irreversibly catalyze the opposite reaction involved in glycolysis. These three enzymes, as well as six other glycolytic/gluconeogenic enzymes, are located in peroxisome-related organelles, named glycosomes. Incorporation of 13C-enriched glycerol (a more effective alternative to proline for monitoring gluconeogenic activity) into F6P and G6P was more affected in the PFK null mutant than in the FBPase null mutant, suggesting the PFK contributes at least as much as FBPase to gluconeogenesis. We also showed that glucose deprivation did not affect the quantities of PFK substrates and products, whereas an approximately 500-fold increase in the substrate/product ratio was expected for PFK to carry out the gluconeogenic reaction. In conclusion, we show for the first time that ATP-dependent PFK can function in vivo in the gluconeogenic direction, even in the presence of FBPase activity. This particular feature, which precludes loss of ATP through a futile cycle involving PFK and FBPase working simultaneously in the glycolytic and gluconeogenic directions, respectively, is possibly due to the supramolecular organization of the metabolic pathway within glycosomes to overcome thermodynamic barriers through metabolic channeling.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3002938"},"PeriodicalIF":9.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of gene expression within individual cells reveals spatiotemporal patterns underlying Vibrio cholerae biofilm development. 单个细胞内基因表达的分析揭示了霍乱弧菌生物膜发育的时空模式。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-16 DOI: 10.1371/journal.pbio.3003187
Grace E Johnson, Chenyi Fei, Ned S Wingreen, Bonnie L Bassler
{"title":"Analysis of gene expression within individual cells reveals spatiotemporal patterns underlying Vibrio cholerae biofilm development.","authors":"Grace E Johnson, Chenyi Fei, Ned S Wingreen, Bonnie L Bassler","doi":"10.1371/journal.pbio.3003187","DOIUrl":"10.1371/journal.pbio.3003187","url":null,"abstract":"<p><p>Bacteria commonly exist in multicellular, surface-attached communities called biofilms. Biofilms are central to ecology, medicine, and industry. The Vibrio cholerae pathogen forms biofilms from single founder cells that, via cell division, mature into three-dimensional structures with distinct, yet reproducible, regional architectures. To define mechanisms underlying biofilm developmental transitions, we establish a single-molecule fluorescence in situ hybridization (smFISH) approach that enables accurate quantitation of spatiotemporal gene-expression patterns in biofilms at cell-scale resolution. smFISH analyses of V. cholerae biofilm regulatory and structural genes demonstrate that, as biofilms mature, overall matrix gene expression decreases, and simultaneously, a pattern emerges in which matrix gene expression becomes largely confined to peripheral biofilm cells. Both quorum sensing and c-di-GMP-signaling are required to generate the proper temporal pattern of matrix gene expression. Quorum sensing signaling is uniform across the biofilm, and thus, c-di-GMP-signaling alone sets the regional matrix gene expression pattern. The smFISH strategy provides insight into mechanisms conferring particular fates to individual biofilm cells.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003187"},"PeriodicalIF":9.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is pathogen prediction possible? 病原体预测可能吗?
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-15 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003162
Arturo Casadevall
{"title":"Is pathogen prediction possible?","authors":"Arturo Casadevall","doi":"10.1371/journal.pbio.3003162","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003162","url":null,"abstract":"<p><p>As humanity comes into contact with new microbes, there is a need to identify which might be future pathogenic threats. Host-microbe interactions manifest emergent properties and chaotic dynamics, posing limits on prediction. However, probabilistic predictions are possible.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003162"},"PeriodicalIF":9.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular states underlying neuronal cell type development and plasticity in the postnatal whisker cortex. 出生后须皮层神经元细胞类型发育和可塑性的分子状态。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-14 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003176
Salwan Butrus, Hannah R Monday, Christopher J Yoo, Daniel E Feldman, Karthik Shekhar
{"title":"Molecular states underlying neuronal cell type development and plasticity in the postnatal whisker cortex.","authors":"Salwan Butrus, Hannah R Monday, Christopher J Yoo, Daniel E Feldman, Karthik Shekhar","doi":"10.1371/journal.pbio.3003176","DOIUrl":"10.1371/journal.pbio.3003176","url":null,"abstract":"<p><p>Mouse whisker somatosensory cortex (wS1) is a major model system to study the experience-dependent plasticity of cortical neuron physiology, morphology, and sensory coding. However, the role of sensory experience in regulating neuronal cell type development and gene expression in wS1 remains poorly understood. We assembled a transcriptomic atlas of wS1 during postnatal development comprising 45 molecularly distinct neuronal types that can be grouped into eight excitatory and four inhibitory neuron subclasses. Between postnatal day (P) 12, the onset of active whisking, and P22, when classical critical periods close, ~ 250 genes were regulated in a neuronal subclass-specific fashion when whisker experience was normal. At the resolution of neuronal types, only the composition of layer (L) 2/3 glutamatergic neurons, but not other neuronal types, changed substantially between P12 and P22. These postnatal compositional changes in L2/3 neuronal types resemble those observed previously in the primary visual cortex (V1), and the temporal gene expression changes were also highly conserved between the regions. Unlike V1, however, cell type maturation in wS1 is not substantially dependent on sensory experience, as 10-day full-face whisker deprivation from P12 to P22 did not influence the transcriptomic identity nor composition of L2/3 neuronal types. A one-day competitive whisker deprivation protocol from P21 to P22 also did not affect cell type identity but induced moderate changes in plasticity-related gene expression. Thus, developmental maturation of cell types is similar in V1 and wS1, but sensory deprivation minimally affects cell type development in wS1.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003176"},"PeriodicalIF":9.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension. 磷酸酶独立的平滑肌钙调神经磷酸酶的活性协调导致高血压的基因表达程序。
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-05-14 DOI: 10.1371/journal.pbio.3003163
Paula Sofía Yunes-Leites, Yilin Sun, Sara Martínez-Martínez, Álvaro Alfayate, Marta Toral, María José Méndez-Olivares, Ángel Colmenar, Ana Isabel Torralbo, Dolores López-Maderuelo, Sergio Mateos-García, David N Cornfield, Jesús Vázquez, Juan Miguel Redondo, Miguel R Campanero
{"title":"Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension.","authors":"Paula Sofía Yunes-Leites, Yilin Sun, Sara Martínez-Martínez, Álvaro Alfayate, Marta Toral, María José Méndez-Olivares, Ángel Colmenar, Ana Isabel Torralbo, Dolores López-Maderuelo, Sergio Mateos-García, David N Cornfield, Jesús Vázquez, Juan Miguel Redondo, Miguel R Campanero","doi":"10.1371/journal.pbio.3003163","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003163","url":null,"abstract":"<p><p>Angiotensin-II (Ang-II) drives pathological vascular wall remodeling in hypertension and abdominal aortic aneurysm (AAA) through mechanisms that are not completely understood. Previous studies showed that the phosphatase activity of calcineurin (Cn) mediates Ang-II-induced AAA, but the cell type involved in the action of Cn in AAA formation remained unknown. Here, by employing newly created smooth muscle cell (SMC)-specific and endothelial cell (EC)-specific Cn-deficient mice (SM-Cn-/- and EC-Cn-/- mice), we show that Cn expressed in SMCs, but not ECs, was required for Ang-II-induced AAA. Unexpectedly, SMC Cn also played a structural role in the early onset and maintenance of Ang-II-induced hypertension, independently of its known phosphatase activity. Among the signaling pathways activated by Ang-II, Cn signaling is essential in SMCs, as nearly 90% of the genes regulated by Ang-II in the aorta required Cn expression in SMCs. Cn orchestrated, independently of its enzymatic activity, the induction by Ang-II of a transcriptional program closely related to SMC contractility and hypertension. Cn deletion in SMCs, but not its pharmacological inhibition, impaired the regulation of arterial contractility. Among the genes whose regulation by Ang-II required Cn expression but not its phosphatase activity, we discovered that Serpine1 was critical for Ang-II-induced hypertension. Indeed, pharmacological inhibition of PAI-1, the protein encoded by Serpine1, impaired SMCs contractility and readily regressed hypertension. Mechanistically, Serpine1 induction was mediated by Smad2 activation via the structural role of Cn. These findings uncover an unexpected role for Cn in vascular pathophysiology and highlight PAI-1 as a potential therapeutic target for hypertension.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003163"},"PeriodicalIF":9.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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