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Inhaled DNAI1 mRNA therapy for treatment of primary ciliary dyskinesia 吸入dnai1mrna治疗原发性纤毛运动障碍
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 : 2025-04-28 DOI: 10.1073/pnas.2421915122
Mirko Hennig, Rumpa B. Bhattacharjee, Ishita Agarwal, Ali Alfaifi, Jade E. Casillas, Sofia Chavez, Daniella Ishimaru, David Liston, Sakya Mohapatra, Touhidul Molla, Suyog Pathare, Maninder S. Sidhu, Peng Wang, Zechen Wang, T. Noelle Lombana, Vladimir G. Kharitonov, Jessica A. Couch, David J. Lockhart, Brandon A. Wustman
{"title":"Inhaled DNAI1 mRNA therapy for treatment of primary ciliary dyskinesia","authors":"Mirko Hennig, Rumpa B. Bhattacharjee, Ishita Agarwal, Ali Alfaifi, Jade E. Casillas, Sofia Chavez, Daniella Ishimaru, David Liston, Sakya Mohapatra, Touhidul Molla, Suyog Pathare, Maninder S. Sidhu, Peng Wang, Zechen Wang, T. Noelle Lombana, Vladimir G. Kharitonov, Jessica A. Couch, David J. Lockhart, Brandon A. Wustman","doi":"10.1073/pnas.2421915122","DOIUrl":"https://doi.org/10.1073/pnas.2421915122","url":null,"abstract":"Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder caused by mutations in one of at least 50 different genes that encode proteins involved in the biogenesis, structure, or function of motile cilia. Genetically inherited defects in motile cilia cause PCD, a debilitating respiratory disease for which there is no approved therapy. The dynein axonemal intermediate chain 1 (DNAI1) protein is a key structural element of the ciliary outer dynein arm (ODA) critical for normal ciliary activity and subsequent clearance of mucus from the conducting airways in humans. Loss-of-function mutations in DNAI1 account for up to 10% of all PCD cases, with functional abnormalities in patients presenting at or near birth and leading to a life-long course of disability, including progressive loss of lung function and bronchiectasis by adulthood. This underscores the significant unmet need for disease-modifying treatments that restore ciliary activity and mucociliary clearance in PCD patients. In this work, we demonstrate that lipid nanoparticle (LNP)-formulated human <jats:italic>DNAI1</jats:italic> mRNA can be delivered as an aerosol to primary human bronchial epithelial cell models and to nonhuman primate (NHP) lungs. Additionally, we show that delivery of aerosolized LNP- <jats:italic>DNAI1</jats:italic> mRNA to NHPs leads to detectable levels of newly translated human DNAI1 protein, at doses that overlap with exposures in an in vitro cell-based PCD model enabling rescue of ciliary function. Therefore, these data support further development of the inhaled <jats:italic>DNAI1</jats:italic> mRNA therapy in clinical studies as a potential disease-modifying treatment for PCD.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"7 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884756","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
Dopamine induces fear extinction by activating the reward-responding amygdala neurons 多巴胺通过激活奖励反应的杏仁核神经元来诱导恐惧消退
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 : 2025-04-28 DOI: 10.1073/pnas.2501331122
Xiangyu Zhang, Katelyn Flick, Marianna Rizzo, Michele Pignatelli, Susumu Tonegawa
{"title":"Dopamine induces fear extinction by activating the reward-responding amygdala neurons","authors":"Xiangyu Zhang, Katelyn Flick, Marianna Rizzo, Michele Pignatelli, Susumu Tonegawa","doi":"10.1073/pnas.2501331122","DOIUrl":"https://doi.org/10.1073/pnas.2501331122","url":null,"abstract":"The extinction of conditioned fear responses is crucial for adaptive behavior, and its impairment is a hallmark of anxiety disorders such as posttraumatic stress disorder. Fear extinction takes place when animals form a new memory that suppresses the original fear memory. In the case of context-dependent fear memory, the new memory is formed within the reward-responding posterior subset of basolateral amygdala (BLA) that is genetically marked by <jats:italic> Ppp1r1b <jats:sup>+</jats:sup> </jats:italic> neurons. These memory engram cells suppress the activity of the original fear-responding <jats:italic> Rspo2 <jats:sup>+</jats:sup> </jats:italic> engram cells present in the anterior BLA, hence fear extinction. However, the neurological nature of the teaching signal that instructs the formation of fear extinction memory in the <jats:italic> Ppp1r1b <jats:sup>+</jats:sup> </jats:italic> neurons is unknown. Here, we demonstrate that ventral tegmental area (VTA) dopaminergic signaling drives fear extinction in distinct BLA neuronal populations. We show that BLA fear and extinction neuronal populations receive topographically divergent inputs from VTA dopaminergic neurons via differentially expressed dopamine receptors. Fiber photometry recordings of dopaminergic activity in the BLA reveal that dopamine (DA) activity is time-locked to freezing cessation in BLA fear extinction neurons, but not BLA fear neurons. Furthermore, this dopaminergic activity in BLA fear extinction neurons correlates with extinction learning. Finally, using projection-specific optogenetic manipulation, we find that activation of the VTA DA projections to BLA reward and fear neurons accelerated or impaired fear extinction, respectively. Together, this work demonstrates that dopaminergic activity bidirectionally controls fear extinction by distinct patterns of activity at BLA fear and extinction neurons.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"45 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884758","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
Dysregulation of MYBL2 impairs extravillous trophoblast lineage development and function, contributing to recurrent spontaneous abortion MYBL2的失调会损害外滋养细胞谱系的发育和功能,导致复发性自然流产
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 : 2025-04-28 DOI: 10.1073/pnas.2421653122
Zhi-Hong Wu, Cen Yi, En-Xiang Chen, Jia-Qi Xu, Cong Li, Lu Yao, Fang-Fang Li, Li-Juan Fu, Lu-Xing Ge, Ying-Xiong Wang, You-Long Xie, Yu-Bin Ding, Jing Tang
{"title":"Dysregulation of MYBL2 impairs extravillous trophoblast lineage development and function, contributing to recurrent spontaneous abortion","authors":"Zhi-Hong Wu, Cen Yi, En-Xiang Chen, Jia-Qi Xu, Cong Li, Lu Yao, Fang-Fang Li, Li-Juan Fu, Lu-Xing Ge, Ying-Xiong Wang, You-Long Xie, Yu-Bin Ding, Jing Tang","doi":"10.1073/pnas.2421653122","DOIUrl":"https://doi.org/10.1073/pnas.2421653122","url":null,"abstract":"Recurrent spontaneous abortion (RSA) is a pregnancy-related condition characterized by a complex etiology. While placental trophoblast dysfunction is strongly associated with the development and progression of RSA, the underlying molecular mechanisms remain poorly understood. In this study, we observed a significant decrease in the expression of MYB Proto-Oncogene Like 2 (MYBL2) in the villous tissue of patients with RSA and the placentas of abortion-prone (AP) mice. Utilizing human trophoblast stem cells (hTSCs), we identified MYBL2 as a critical regulator of hTSCs stemness maintenance, promoting the expression of the stemness-associated genes Tumor protein p63 (TP63) and TEA Domain Transcription Factor 4 (TEAD4). Furthermore, MYBL2 facilitates the differentiation of hTSCs into extravillous trophoblast (EVT) by positively regulating Ajuba LIM Protein (AJUBA) expression. Using HTR-8/SVneo cell line, an immortalized EVT-like model, we found that MYBL2 positively regulates AJUBA expression by binding to the distal region of the AJUBA promoter. Additionally, the MYBL2–AJUBA axis enhances the migration and invasion of HTR-8/SVneo cells by suppressing the Hippo signaling pathway. Our study indicates that the dysregulation of MYBL2 expression in placental trophoblasts is associated with the pathogenesis of RSA, highlighting its potential as a therapeutic target for this condition.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"140 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884763","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
A twist grain boundary phase in aqueous solutions of the nucleic acid tetramer GTAC 核酸四聚体GTAC水溶液中的扭转晶界相
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 : 2025-04-28 DOI: 10.1073/pnas.2416142122
Gregory P. Smith, Chenhui Zhu, Mikail Zernenkov, Guillaume Frechet, Noel A. Clark
{"title":"A twist grain boundary phase in aqueous solutions of the nucleic acid tetramer GTAC","authors":"Gregory P. Smith, Chenhui Zhu, Mikail Zernenkov, Guillaume Frechet, Noel A. Clark","doi":"10.1073/pnas.2416142122","DOIUrl":"https://doi.org/10.1073/pnas.2416142122","url":null,"abstract":"At high concentration, long Watson/Crick (WC) double-helixed DNA forms columnar crystal or liquid crystal phases of linear, parallel duplex chains packed on periodic lattices. This can also be a structural motif of short NA oligomers such as the 5’-GTAC-3’ studied here, which makes four-base WC duplexes having hydrophobic blunt ends. End-to-end aggregation then assembles these duplexes into columns and columnar phases are stabilized, in spite of breaks in the double helix every four bases. But the new degrees of freedom introduced by such breaks also enable opportunities for a more diverse palette of self-assembly modes, producing striking self-assemblies of DNA that would not be achievable with contiguous polymers. These include recently reported three-dimensional (3D) periodic low-density nanoscale networks of GCCG, and the twist grain boundary (TGB) phase presented here. In the TGB, columns of GTAC pairs assemble into monolayer sheets in which the duplex columns are mutually parallel. However, unlike in the columnar crystals, these sheets stack in helical fashion into lamellar arrays in which the column axis of each layer is rotated through a 60° angle with respect to the columns in neighboring layers. This assembly of DNA is unique in that it the fills a 3D volume wherein the major grooves of columns in each layer mutually enter and interlock with the major grooves of columns in neighboring layers. This locking is optimized by small adjustments in structure enabled by the breaks in the duplex backbones.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"19 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884769","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
Anatomy of the magmatic–hydrothermal system beneath Uturuncu volcano, Bolivia, by joint seismological and petrophysical analysis 玻利维亚Uturuncu火山岩浆-热液系统的地震学和岩石物理联合分析
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 : 2025-04-28 DOI: 10.1073/pnas.2420996122
Ying Liu, John Michael Kendall, Haijiang Zhang, Jonathan D. Blundy, Matthew E. Pritchard, Thomas Hudson, Patricia MacQueen
{"title":"Anatomy of the magmatic–hydrothermal system beneath Uturuncu volcano, Bolivia, by joint seismological and petrophysical analysis","authors":"Ying Liu, John Michael Kendall, Haijiang Zhang, Jonathan D. Blundy, Matthew E. Pritchard, Thomas Hudson, Patricia MacQueen","doi":"10.1073/pnas.2420996122","DOIUrl":"https://doi.org/10.1073/pnas.2420996122","url":null,"abstract":"For a volcanic system, evaluating potential eruption probability requires understanding the extent of melt and gas accumulation in the upper crustal reservoir, which is challenging to resolve. Here, we jointly use geophysical imaging and petrophysical analysis to unravel the current state and pathway of gas or supercritical fluids in the upper crust beneath Uturuncu volcano in Bolivia. Although it last erupted 250 ± 5 ka ago, Uturuncu remains active with observable deformation and seismicity. To assess its current state, we have determined high-resolution isotropic and anisotropic seismic velocity structures of the volcanic system in the upper crust using local seismic networks. Combining our seismic analysis with previous geophysical imaging results and rock physics modeling, we delineate pathways of migrating fluids traveling toward the surface and a shallow gas accumulation zone beneath the crater. This fluid migration and accumulation explains why Uturuncu volcano still shows signs of activity. Our study exemplifies how seismology combined with rock physics models and petrological analysis can resolve the detailed structure and composition of a volcanic system, critical for assessing eruption hazard.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"7 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884891","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
Radiation protection and structural stability of fungal melanin polylactic acid biocomposites in low Earth orbit 真菌黑色素-聚乳酸生物复合材料近地轨道辐射防护及结构稳定性研究
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 : 2025-04-28 DOI: 10.1073/pnas.2427118122
Radames J. B. Cordero, Kim K. de Groh, Quigly Dragotakes, Saranshu Singla, Christopher Maurer, Andrew Trunek, Arlene Chiu, Jonghyun Hwang, Sylvie Crowell, Theresa Benyo, Susanna M. Thon, Lynn J. Rothschild, Ali Dhinojwala, Arturo Casadevall
{"title":"Radiation protection and structural stability of fungal melanin polylactic acid biocomposites in low Earth orbit","authors":"Radames J. B. Cordero, Kim K. de Groh, Quigly Dragotakes, Saranshu Singla, Christopher Maurer, Andrew Trunek, Arlene Chiu, Jonghyun Hwang, Sylvie Crowell, Theresa Benyo, Susanna M. Thon, Lynn J. Rothschild, Ali Dhinojwala, Arturo Casadevall","doi":"10.1073/pnas.2427118122","DOIUrl":"https://doi.org/10.1073/pnas.2427118122","url":null,"abstract":"Materials in low Earth orbit (LEO) face radiation, atomic oxygen erosion, and extreme temperature fluctuations, which can severely compromise their structural and functional integrity. Developing lightweight, multifunctional materials capable of withstanding these harsh conditions is critical for long-term space exploration and sustainable extraterrestrial settlements. This study evaluates the structural stability and radiation shielding efficacy of polylactic acid (PLA) and biocomposites, including PLA infused with fungal melanin, synthetic melanin, or animal melanin, and a compressed mycelium (CMy) coated with PLA (PLA-CMy), after exposure to the LEO environment. Samples were deployed on the Materials International Space Station Experiment–Flight Facility platform for approximately 6 mo in zenith- and wake-facing orientations. Postflight analyses comparing flight-exposed samples to Earth controls revealed composition- and orientation-dependent differences in mass loss, optical properties, and surface morphology. Notably, fungal melanin reduced mass loss and surface wrinkle formation, indicating a protective effect against PLA degradation in LEO. Biocomposites also demonstrated shielding effects by protecting an underlying polyvinyl chloride backing layer from damage. These findings demonstrate PLA’s performance in space and highlight fungal melanin as a bioderived additive to enhance PLA resilience under LEO conditions, advancing the development of sustainable materials for future space missions.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"138 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884752","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
Ultrasound-activated cilia for biofilm control in indwelling medical devices 超声激活纤毛在留置医疗器械生物膜控制中的应用
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 : 2025-04-28 DOI: 10.1073/pnas.2418938122
Pedro Amado, Cornel Dillinger, Chaimae Bahou, Ali Hashemi Gheinani, Dominik Obrist, Fiona Burkhard, Daniel Ahmed, Francesco Clavica
{"title":"Ultrasound-activated cilia for biofilm control in indwelling medical devices","authors":"Pedro Amado, Cornel Dillinger, Chaimae Bahou, Ali Hashemi Gheinani, Dominik Obrist, Fiona Burkhard, Daniel Ahmed, Francesco Clavica","doi":"10.1073/pnas.2418938122","DOIUrl":"https://doi.org/10.1073/pnas.2418938122","url":null,"abstract":"Biofilm formation and encrustation are major issues in indwelling medical devices, such as urinary stents and catheters, as they lead to blockages and infections. Currently, to limit these effects, frequent replacements of these devices are necessary, resulting in a significant reduction in patients’ quality of life and an increase in healthcare costs. To address these challenges, by leveraging recent advancements in robotics and microfluidic technologies, we envision a self-cleaning system for indwelling medical devices equipped with bioinspired ultrasound-activated cilia. These cilia could be regularly activated transcutaneously by ultrasound, generating steady streaming, which can be used to remove encrusted deposits. In this study, we tested the hypothesis that the generated streaming can efficiently remove encrustations and biofilm from surfaces. To this end, we developed a microfluidic model featuring ultrasound-activated cilia on its wall. We showed that upon ultrasound activation, the cilia generated intense, steady streaming, reaching fluid velocity up to 10 mm/s. In all our experiments, this mechanism was able to efficiently clean typical encrustation (calcium carbonate and oxalate) and biofilm found in urological devices. The generated shear forces released, broke apart, and flushed away encrusted deposits. These findings suggest a broad potential for ultrasound-activated cilia in the maintenance of various medical devices. Compared to existing methods, our approach could reduce the need for invasive procedures, potentially lowering infection risks and enhancing patient comfort.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"17 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884757","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
A hierarchy of processing complexity and timescales for natural sounds in the human auditory cortex 人类听觉皮层处理自然声音的复杂性和时间尺度的层次结构
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 : 2025-04-28 DOI: 10.1073/pnas.2412243122
Kyle M. Rupp, Jasmine L. Hect, Emily E. Harford, Lori L. Holt, Avniel Singh Ghuman, Taylor J. Abel
{"title":"A hierarchy of processing complexity and timescales for natural sounds in the human auditory cortex","authors":"Kyle M. Rupp, Jasmine L. Hect, Emily E. Harford, Lori L. Holt, Avniel Singh Ghuman, Taylor J. Abel","doi":"10.1073/pnas.2412243122","DOIUrl":"https://doi.org/10.1073/pnas.2412243122","url":null,"abstract":"Efficient behavior is supported by humans’ ability to rapidly recognize acoustically distinct sounds as members of a common category. Within the auditory cortex, critical unanswered questions remain regarding the organization and dynamics of sound categorization. We performed intracerebral recordings during epilepsy surgery evaluation as 20 patient-participants listened to natural sounds. We then built encoding models to predict neural responses using sound representations extracted from different layers within a deep neural network (DNN) pretrained to categorize sounds from acoustics. This approach yielded accurate models of neural responses throughout the auditory cortex. The complexity of a cortical site’s representation (measured by the depth of the DNN layer that produced the best model) was closely related to its anatomical location, with shallow, middle, and deep layers associated with core (primary auditory cortex), lateral belt, and parabelt regions, respectively. Smoothly varying gradients of representational complexity existed within these regions, with complexity increasing along a posteromedial-to-anterolateral direction in core and lateral belt and along posterior-to-anterior and dorsal-to-ventral dimensions in parabelt. We then characterized the time (relative to sound onset) when feature representations emerged; this measure of temporal dynamics increased across the auditory hierarchy. Finally, we found separable effects of region and temporal dynamics on representational complexity: sites that took longer to begin encoding stimulus features had higher representational complexity independent of region, and downstream regions encoded more complex features independent of temporal dynamics. These findings suggest that hierarchies of timescales and complexity represent a functional organizational principle of the auditory stream underlying our ability to rapidly categorize sounds.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"82 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884759","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
Bone microstructure supports a Mesozoic origin for a semiaquatic burrowing lifestyle in monotremes (Mammalia) 骨骼微观结构支持单孔目动物(哺乳动物)半水生穴居生活方式的中生代起源
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 : 2025-04-28 DOI: 10.1073/pnas.2413569122
Suzanne J. Hand, Laura A. B. Wilson, Camilo López-Aguirre, Alexandra Houssaye, Michael Archer, Joseph J. Bevitt, Alistair R. Evans, Amalia Y. Halim, Tzong Hung, Thomas H. Rich, Patricia Vickers-Rich, Robin M. D. Beck
{"title":"Bone microstructure supports a Mesozoic origin for a semiaquatic burrowing lifestyle in monotremes (Mammalia)","authors":"Suzanne J. Hand, Laura A. B. Wilson, Camilo López-Aguirre, Alexandra Houssaye, Michael Archer, Joseph J. Bevitt, Alistair R. Evans, Amalia Y. Halim, Tzong Hung, Thomas H. Rich, Patricia Vickers-Rich, Robin M. D. Beck","doi":"10.1073/pnas.2413569122","DOIUrl":"https://doi.org/10.1073/pnas.2413569122","url":null,"abstract":"The platypus and four echidna species are the only living egg-laying mammals and the sole extant representatives of Order Monotremata. The platypus and echidnas are very disparate both morphologically and ecologically: The platypus is a specialized semiaquatic burrowing form that forages for freshwater invertebrates, whereas echidnas are fully terrestrial and adapted for feeding on social insects and earthworms. It has been proposed that echidnas evolved from a semiaquatic, platypus-like ancestor, but fossil evidence for such a profound evolutionary transformation has been lacking, and this hypothesis remains controversial. Here, we present original data about the Early Cretaceous (108 to 103 Ma) Australian mammal <jats:italic>Kryoryctes cadburyi</jats:italic> , currently only known from a single humerus, that provides key information relating to this question. Phylogenetic analysis of a 536-character morphological matrix of mammaliaforms places <jats:italic>Kryoryctes</jats:italic> as a stem-monotreme. Three-dimensional whole bone comparisons show that the overall shape of the humerus is more similar to that of echidnas than the platypus, but analysis of microstructure reveals specializations found in semiaquatic mammals, including a particularly thick cortex and a highly reduced medullary cavity, present in the platypus but absent in echidnas. The evidence suggests <jats:italic>Kryoryctes</jats:italic> was a semiaquatic burrower, indicating that monotremes first evolved an amphibious lifestyle in the Mesozoic, and providing support for the hypothesis that this is ancestral for living monotremes as a whole. The lineage leading to the modern platypus appears to have been characterized by extremely long term (&gt;100 My) niche conservatism, with echidnas representing a much later reversion to a fully terrestrial lifestyle.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"52 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884892","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
Cryptic genetic variation in brain gene expression precedes the evolution of cannibalism in spadefoot toad tadpoles 脑基因表达的隐性遗传变异先于爪蟾蝌蚪同类相食的进化
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 : 2025-04-28 DOI: 10.1073/pnas.2418431122
Dante J. Nesta, Cristina C. Ledón-Rettig
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