SciencePub Date : 2024-12-20Epub Date: 2024-12-19DOI: 10.1126/science.adr8187
Mahdi Chegnizadeh, Marco Scigliuzzo, Amir Youssefi, Shingo Kono, Evgenii Guzovskii, Tobias J Kippenberg
{"title":"Quantum collective motion of macroscopic mechanical oscillators.","authors":"Mahdi Chegnizadeh, Marco Scigliuzzo, Amir Youssefi, Shingo Kono, Evgenii Guzovskii, Tobias J Kippenberg","doi":"10.1126/science.adr8187","DOIUrl":"https://doi.org/10.1126/science.adr8187","url":null,"abstract":"<p><p>Collective phenomena arise from interactions within complex systems, leading to behaviors absent in individual components. Observing quantum collective phenomena with macroscopic mechanical oscillators has been impeded by the stringent requirement that oscillators be identical. We demonstrate the quantum regime for collective motion of <i>N</i> = 6 mechanical oscillators, a hexamer, in a superconducting circuit optomechanical platform. By increasing the optomechanical couplings, the system transitions from individual to collective motion, characterized by a [Formula: see text] enhancement of cavity-collective mode coupling, akin to superradiance of atomic ensembles. Using sideband cooling, we prepare the collective mode in the quantum ground state and measure its quantum sideband asymmetry, with zero-point motion distributed across distant oscillators. This regime of optomechanics opens avenues for studying multipartite entanglement, with potential advances in quantum metrology.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"386 6728","pages":"1383-1388"},"PeriodicalIF":44.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865563","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.adk6583
Justin Joachim, Davide Maselli, Emmanouela Petsolari, Jurjan Aman, Pamela Swiatlowska, David Killock, Hiba Chaudhry, Ali A. Zarban, Mosharraf Sarker, Paul Fraser, Simon J. Cleary, Richard Amison, Isabelle Cuthbert, Yue Yang, Magda Meier, Franca Fraternali, Susan D. Brain, Ajay M. Shah, Aleksandar Ivetic
{"title":"TNIK: A redox sensor in endothelial cell permeability","authors":"Justin Joachim, Davide Maselli, Emmanouela Petsolari, Jurjan Aman, Pamela Swiatlowska, David Killock, Hiba Chaudhry, Ali A. Zarban, Mosharraf Sarker, Paul Fraser, Simon J. Cleary, Richard Amison, Isabelle Cuthbert, Yue Yang, Magda Meier, Franca Fraternali, Susan D. Brain, Ajay M. Shah, Aleksandar Ivetic","doi":"10.1126/sciadv.adk6583","DOIUrl":"https://doi.org/10.1126/sciadv.adk6583","url":null,"abstract":"Dysregulation of endothelial barrier integrity can lead to vascular leak and potentially fatal oedema. TNF-α controls endothelial permeability during inflammation and requires the actin organizing Ezrin-Radixin-Moesin (ERM) proteins. We identified TRAF2 and NCK-interacting kinase (TNIK) as a kinase directly phosphorylating and activating ERM, specifically at the plasma membrane of primary human endothelial cells. TNIK mediates TNF-α–dependent cellular stiffness and paracellular gap formation in vitro and is essential in driving inflammatory oedema formation in vivo. Unlike its homologs, TNIK activity is negatively and reversibly regulated by H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> -mediated oxidation of C202 within the kinase domain. TNIK oxidation results in intermolecular disulfide bond formation and loss of kinase activity. Pharmacologic inhibition of endogenous reactive oxygen species production in endothelial cells elevated TNIK-dependent ERM phosphorylation, endothelial cell contraction, and cell rounding. Together, we highlight an interplay between TNIK, ERM phosphorylation, and redox signalling in regulating TNF-induced endothelial cell permeability.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"90 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867144","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.adr2135
Shan Zhou, Fenglin Chen, Ziyang Cheng, Can Gao, Zengyi He, Shutao Wang, Lei Jiang, Haoyu Dai, Zhichao Dong
{"title":"Rapid water drainage on human eyelashes of a hydrophobic Brachistochrone fiber array","authors":"Shan Zhou, Fenglin Chen, Ziyang Cheng, Can Gao, Zengyi He, Shutao Wang, Lei Jiang, Haoyu Dai, Zhichao Dong","doi":"10.1126/sciadv.adr2135","DOIUrl":"https://doi.org/10.1126/sciadv.adr2135","url":null,"abstract":"Numerous organisms exploit asymmetrical capillary forces generated by unique fiber or asymmetrical tapered structures to rapidly eliminate undesired liquid for survival in moist or rainy habitats. Human eyelashes, the primary protector of eyes, use a yet-to-be-fully-understood mechanism to efficiently transfer incoming liquid for vision safeguarding. Here, we elucidate that human eyelashes featuring a hydrophobic curved flexible fiber array with surface micro-ratchet and macro-curvature approximating the <jats:italic>Brachistochrone</jats:italic> is adept at directionally and rapidly expelling incoming liquid to maintain clear vision. These structural attributes are sequentially used for liquid drainage, starting from anisotropic retention via micro-ratchet, followed by the elastic expulsion among deflected hydrophobic flexible fiber arrays and culminating in the fastest sliding off along a <jats:italic>Brachistochrone</jats:italic> path, which together reduce the contact time by about 20% of that on rigid linear slopes. Investigating the intricate relationship between multistructure and draining efficiency of human eyelashes may inspire the design of advanced liquid-repelling edges on outdoor devices to maintain dryness.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"31 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867201","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.adn8255
Danchen Jia, Ran Cheng, James H. McNeely, Haonan Zong, Xinyan Teng, Xinxin Xu, Ji-Xin Cheng
{"title":"Ultrasensitive infrared spectroscopy via vibrational modulation of plasmonic scattering from a nanocavity","authors":"Danchen Jia, Ran Cheng, James H. McNeely, Haonan Zong, Xinyan Teng, Xinxin Xu, Ji-Xin Cheng","doi":"10.1126/sciadv.adn8255","DOIUrl":"https://doi.org/10.1126/sciadv.adn8255","url":null,"abstract":"Most molecules and dielectric materials have characteristic bond vibrations or phonon modes in the mid-infrared regime. However, infrared absorption spectroscopy lacks the sensitivity for detecting trace analytes due to the low quantum efficiency of infrared sensors. Here, we report mid-infrared photothermal plasmonic scattering (MIP-PS) spectroscopy to push the infrared detection limit toward nearly a hundred molecules in a plasmonic nanocavity. The plasmon scattering from a nanoparticle-on-film cavity has extremely high sensitivity to the spacing defined by the analyte molecules inside the nanogap. Meanwhile, a 1000-fold infrared light intensity enhancement at the bond vibration frequency further boosts the interaction between mid-IR photons and analyte molecules. MIP-PS spectroscopic detection of nitrile or nitro group in ~130 molecules was demonstrated. This method heralds potential in ultrasensitive bond-selective biosensing and bioimaging.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"24 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867261","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.adr2225
Marc Meredith, Michael Morse, Amaya Madarang, Katie Steele
{"title":"Measuring lost votes by mail","authors":"Marc Meredith, Michael Morse, Amaya Madarang, Katie Steele","doi":"10.1126/sciadv.adr2225","DOIUrl":"https://doi.org/10.1126/sciadv.adr2225","url":null,"abstract":"The rise of mail balloting has led to concerns that procedural requirements can lead to “lost votes by mail.” We theorize how procedural requirements can affect the incidence and form of lost votes and highlight three measurement issues with equating lost votes and rejected mail ballots. First, coverage: Not all rejected mail ballots are documented. Second, substitution: Some people whose mail ballot is rejected may subsequently successfully vote, in particular if they were notified in time to take action. Third, deterrence: Others may not return their mail ballots if they expect them to be rejected. While rejected mail ballots could over- or underestimate lost votes, a case study of Pennsylvania’s 2022 general election reveals at least 47% more lost votes than rejected mail ballots. These lost votes could prove electorally consequential in Pennsylvania given the number of mail ballots cast and the substantial partisan splits on mail versus in-person ballots.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"7 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867288","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.adp3954
Zhi Su, Weizhen Zhang, Yu Shi, Tao Cui, Yongchang Xu, Runshi Yang, Man Huang, Chun Zhou, Huimin Zhang, Ting Lu, Jiuxin Qu, Zheng-Guo He, Jianhua Gan, Youjun Feng
{"title":"A bacterial methyltransferase that initiates biotin synthesis, an attractive anti-ESKAPE druggable pathway","authors":"Zhi Su, Weizhen Zhang, Yu Shi, Tao Cui, Yongchang Xu, Runshi Yang, Man Huang, Chun Zhou, Huimin Zhang, Ting Lu, Jiuxin Qu, Zheng-Guo He, Jianhua Gan, Youjun Feng","doi":"10.1126/sciadv.adp3954","DOIUrl":"https://doi.org/10.1126/sciadv.adp3954","url":null,"abstract":"The covalently attached cofactor biotin plays pivotal roles in central metabolism. The top-priority ESKAPE-type pathogens, <jats:italic>Acinetobacter baumannii</jats:italic> and <jats:italic>Klebsiella pneumoniae</jats:italic> , constitute a public health challenge of global concern. Despite the fact that the late step of biotin synthesis is a validated anti-ESKAPE drug target, the primary stage remains fragmentarily understood. We report the functional definition of two BioC isoenzymes (AbBioC for <jats:italic>A. baumannii</jats:italic> and KpBioC for <jats:italic>K. pneumoniae</jats:italic> ) that act as malonyl-ACP methyltransferase and initiate biotin synthesis. The physiological requirement of biotin is diverse within ESKAPE pathogens. CRISPR-Cas9–based inactivation of <jats:italic>bioC</jats:italic> rendered <jats:italic>A. baumannii</jats:italic> and <jats:italic>K. pneumoniae</jats:italic> biotin auxotrophic. The availability of soluble AbBioC enabled the in vitro reconstitution of DTB/biotin synthesis. We solved two crystal structures of AbBioC bound to SAM cofactor (2.54 angstroms) and sinefungin (SIN) inhibitor (1.72 angstroms). Structural and functional study provided molecular basis for SIN inhibition of BioC. We demonstrated that BioC methyltransferase plays dual roles in <jats:italic>K. pneumoniae</jats:italic> infection and <jats:italic>A. baumannii</jats:italic> colistin resistance.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867297","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}
Science AdvancesPub Date : 2024-12-20DOI: 10.1126/sciadv.ads9258
Jae-Hwan Lee, Yoon-Nam Kim, Junsang Lee, Jooik Jeon, Jae-Young Bae, Ju-Yong Lee, Kyung-Sub Kim, Minseong Chae, Hyunjun Park, Jong-hyoung Kim, Kang-Sik Lee, Jeonghyun Kim, Jung Keun Hyun, Daeshik Kang, Seung-Kyun Kang
{"title":"Hypersensitive meta-crack strain sensor for real-time biomedical monitoring","authors":"Jae-Hwan Lee, Yoon-Nam Kim, Junsang Lee, Jooik Jeon, Jae-Young Bae, Ju-Yong Lee, Kyung-Sub Kim, Minseong Chae, Hyunjun Park, Jong-hyoung Kim, Kang-Sik Lee, Jeonghyun Kim, Jung Keun Hyun, Daeshik Kang, Seung-Kyun Kang","doi":"10.1126/sciadv.ads9258","DOIUrl":"https://doi.org/10.1126/sciadv.ads9258","url":null,"abstract":"Real-time monitoring of infinitesimal deformations on complex morphologies is essential for precision biomechanical engineering. While flexible strain sensors facilitate real-time monitoring with shape-adaptive properties, their sensitivity is generally lower than spectroscopic imaging methods. Crack-based strain sensors achieve enhanced sensitivity with gauge factors (GFs) exceeding 30,000; however, such GFs are only attainable at large strains exceeding several percent and decline below 10 for strains under 10 <jats:sup>−3</jats:sup> , rendering them inadequate for minute deformations. Here, we introduce hypersensitive and flexible “meta-crack” sensors detecting infinitesimal strains through previously undiscovered crack-opening mechanisms. These sensors achieve remarkable GFs surpassing 1000 at strains of 10 <jats:sup>−4</jats:sup> on substrates with a Poisson’s ratio of −0.9. The crack orientation–independent gap-widening behavior elucidates the origin of hypersensitivity, corroborated by simplified models and finite element analysis. Additionally, parallel mechanical circuits of meta-cracks effectively address the trade-off between resolution and maximum sensing threshold. In vivo real-time monitoring of cerebrovascular dynamics with a strain resolution of 10 <jats:sup>−5</jats:sup> underscores the hypersensitivity and conformal adaptability of sensors.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"4 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867300","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}
Sandii Constable, Carolyn M. Ott, Andrew L. Lemire, Kevin White, Yu Xun, Amin Lim, Jennifer Lippincott-Schwartz, Saikat Mukhopadhyay
{"title":"Permanent cilia loss during cerebellar granule cell neurogenesis involves withdrawal of cilia maintenance and centriole capping","authors":"Sandii Constable, Carolyn M. Ott, Andrew L. Lemire, Kevin White, Yu Xun, Amin Lim, Jennifer Lippincott-Schwartz, Saikat Mukhopadhyay","doi":"10.1073/pnas.2408083121","DOIUrl":"https://doi.org/10.1073/pnas.2408083121","url":null,"abstract":"Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles. Here, we identify molecular changes that accompany cilia deconstruction and centriole docking in GC neurons. We used single cell transcriptomic and immunocytological analyses to compare the transcript levels and subcellular localization of proteins between progenitor, differentiating, and mature GCs. Differentiating GCs lacked transcripts for key activators of premitotic cilia resorption, indicating that cilia disassembly in differentiating cells is distinct from premitotic cilia resorption. Instead, during differentiation, transcripts of many genes required for cilia maintenance—specifically those encoding components of intraflagellar transport, pericentrosomal material, and centriolar satellites—decreased. The abundance of several corresponding proteins in and around cilia and centrosomes also decreased. These changes coincided with downregulation of SHH signaling prior to differentiation, even in a mutant with excessive SHH activation. Finally, mother centrioles in maturing granule neurons recruited the cap complex protein, CEP97. These data suggest that a global, developmentally programmed decrease in cilium maintenance in differentiating GCs mediates cilia deconstruction, while capping of docked mother centrioles prevents cilia regrowth and dysregulated SHH signaling. Our study provides mechanistic insights expanding our understanding of permanent cilia loss in multiple tissue-specific contexts.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"83 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867588","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}
Science AdvancesPub Date : 2024-12-20Epub Date: 2024-12-18DOI: 10.1126/sciadv.adu9087
Craig E Cameron
{"title":"Ain't no stoppin' us now….","authors":"Craig E Cameron","doi":"10.1126/sciadv.adu9087","DOIUrl":"https://doi.org/10.1126/sciadv.adu9087","url":null,"abstract":"","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 51","pages":"eadu9087"},"PeriodicalIF":11.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855528","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}