Science Advances最新文献_第8页

Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adr9364

Lily Elizabeth R. Feldman, Saswat Mohapatra, Robert T. Jones, Mathijs Scholtes, Charlene B. Tilton, Michael V. Orman, Molishree Joshi, Cailin S. Deiter, Travis P. Broneske, Fangyuan Qu, Corazon Gutierrez, Huihui Ye, Eric T. Clambey, Sarah Parker, Tokameh Mahmoudi, Tahlita Zuiverloon, James C. Costello, Dan Theodorescu

{"title":"Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy","authors":"Lily Elizabeth R. Feldman, Saswat Mohapatra, Robert T. Jones, Mathijs Scholtes, Charlene B. Tilton, Michael V. Orman, Molishree Joshi, Cailin S. Deiter, Travis P. Broneske, Fangyuan Qu, Corazon Gutierrez, Huihui Ye, Eric T. Clambey, Sarah Parker, Tokameh Mahmoudi, Tahlita Zuiverloon, James C. Costello, Dan Theodorescu","doi":"10.1126/sciadv.adr9364","DOIUrl":"https://doi.org/10.1126/sciadv.adr9364","url":null,"abstract":"Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types. We also find the NPEPPS/VRAC gene expression ratio is a predictive measure of cisplatin response in multiple cancer cohorts, showing the broad applicability of this mechanism. Our work describes a specific mechanism of cisplatin resistance, which, given the characteristics of NPEPPS as a drug target, has the potential to improve cancer patient outcomes. In addition, we describe an intracellular mechanism regulating VRAC activity, which is critical for volume regulation in normal cells – a finding with functional implications beyond cancer.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"245 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820587","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

Flexible adjustment of oxytocin neuron activity in mouse dams revealed by microendoscopy

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adt1555

Kasane Yaguchi, Kazunari Miyamichi, Gen-ichi Tasaka

引用次数: 0

Mid-infrared photodetection with 2D metal halide perovskites at ambient temperature

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adk2778

Yanyan Li, Shunran Li, Du Chen, Conrad A. Kocoj, Ankun Yang, Benjamin T. Diroll, Peijun Guo

{"title":"Mid-infrared photodetection with 2D metal halide perovskites at ambient temperature","authors":"Yanyan Li, Shunran Li, Du Chen, Conrad A. Kocoj, Ankun Yang, Benjamin T. Diroll, Peijun Guo","doi":"10.1126/sciadv.adk2778","DOIUrl":"https://doi.org/10.1126/sciadv.adk2778","url":null,"abstract":"The detection of mid-infrared (MIR) light is technologically important for applications such as night vision, imaging, sensing, and thermal metrology. Traditional MIR photodetectors either require cryogenic cooling or have sophisticated device structures involving complex nanofabrication. Here, we conceive spectrally tunable MIR detection by using two-dimensional metal halide perovskites (2D-MHPs) as the critical building block. Leveraging the ultralow cross-plane thermal conductivity and strong temperature-dependent excitonic resonances of 2D-MHPs, we demonstrate ambient-temperature, all-optical detection of MIR light with sensitivity down to 1 nanowatt per square micrometer, using plastic substrates. Through the adoption of membrane-based structures and a photonic enhancement strategy unique to our all-optical detection modality, we further improved the sensitivity to sub–10 picowatt-per-square-micrometer levels. The detection covers the mid-wave infrared regime from 2 to 4.5 micrometers and extends to the long-wave infrared wavelength at 10.6 micrometers, with wavelength-independent sensitivity response. Our work opens a pathway to alternative types of solution-processable, long-wavelength thermal detectors for molecular sensing, environmental monitoring, and thermal imaging.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820620","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

High-throughput single-cell sorting by stimulated Raman-activated cell ejection.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adn6373

Jing Zhang, Haonan Lin, Jiabao Xu, Meng Zhang, Xiaowei Ge, Chi Zhang, Wei E Huang, Ji-Xin Cheng

{"title":"High-throughput single-cell sorting by stimulated Raman-activated cell ejection.","authors":"Jing Zhang, Haonan Lin, Jiabao Xu, Meng Zhang, Xiaowei Ge, Chi Zhang, Wei E Huang, Ji-Xin Cheng","doi":"10.1126/sciadv.adn6373","DOIUrl":"10.1126/sciadv.adn6373","url":null,"abstract":"Raman-activated cell sorting isolates single cells in a nondestructive and label-free manner, but its throughput is limited by small spontaneous Raman scattering cross section. Coherent Raman scattering integrated with microfluidics enables high-throughput cell analysis, but faces challenges with small cells (<3 μm) and tissue sections. Here, we report stimulated Raman-activated cell ejection (S-RACE) that enables high-throughput single-cell sorting by integrating stimulated Raman imaging, in situ image decomposition, and laser-induced cell ejection. S-RACE allows ejection of live bacteria or fungi guided by their Raman signatures. Furthermore, S-RACE successfully sorted lipid-rich Rhodotorula glutinis cells from a cell mixture with a throughput of ~13 cells per second, and the sorting results were confirmed by downstream quantitative polymerase chain reaction. Beyond single cells, S-RACE shows high compatibility with tissue sections. Incorporating a closed-loop feedback control circuit further enables real-time SRS imaging-identification-ejection. In summary, S-RACE opens exciting opportunities for diverse single-cell sorting applications.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadn6373"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assembly and biological functions of metal-biomolecule network nanoparticles formed by metal-phosphonate coordination

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.ads9542

Wanjun Xu, Zhixing Lin, Chan-Jin Kim, Zhaoran Wang, Tianzheng Wang, Christina Cortez-Jugo, Frank Caruso

{"title":"Assembly and biological functions of metal-biomolecule network nanoparticles formed by metal-phosphonate coordination","authors":"Wanjun Xu, Zhixing Lin, Chan-Jin Kim, Zhaoran Wang, Tianzheng Wang, Christina Cortez-Jugo, Frank Caruso","doi":"10.1126/sciadv.ads9542","DOIUrl":"https://doi.org/10.1126/sciadv.ads9542","url":null,"abstract":"Metal-organic networks have attracted widespread interest owing to their hybrid physicochemical properties. Natural biomolecules represent attractive building blocks for these materials because of their inherent biological function and high biocompatibility; however, assembling them into coordination network materials, especially nanoparticles (NPs), is challenging. Herein, we exploit the coordination between metal ions and phosphonate groups, which are present in many biomolecules, to form metal-biomolecule network (MBN) NPs in aqueous solution at room temperature. Various phosphonate-containing biomolecules, including plant phytate, DNA, and proteins, were used to assemble MBN NPs with tunable physicochemical properties (e.g., size). In addition to excellent biocompatibility and high cargo-loading efficiency (>95%), these two-component MBN NPs have various biological functionalities, including endosomal escape, immune regulation, and molecular recognition, thus offering advantages over nonbiomolecular-based coordination materials. This work expands our understanding of metal-organic chemistry with the emerging class of metal-biomolecule systems and provides a pathway for incorporating biofunctionalities into advanced coordination materials for diverse fields.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820570","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

Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq0987

Angeliki Platania, Cathie Erb, Mariano Barbieri, Bastien Molcrette, Erwan Grandgirard, Marit A. C. de Kort, Wim Pomp, Karen Meaburn, Tiegh Taylor, Virlana M. Shchuka, Silvia Kocanova, Mariia Nazarova, Guilherme Monteiro Oliveira, Jennifer A. Mitchell, Evi Soutoglou, Tineke L. Lenstra, Nacho Molina, Argyris Papantonis, Kerstin Bystricky, Tom Sexton

{"title":"Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics","authors":"Angeliki Platania, Cathie Erb, Mariano Barbieri, Bastien Molcrette, Erwan Grandgirard, Marit A. C. de Kort, Wim Pomp, Karen Meaburn, Tiegh Taylor, Virlana M. Shchuka, Silvia Kocanova, Mariia Nazarova, Guilherme Monteiro Oliveira, Jennifer A. Mitchell, Evi Soutoglou, Tineke L. Lenstra, Nacho Molina, Argyris Papantonis, Kerstin Bystricky, Tom Sexton","doi":"10.1126/sciadv.adq0987","DOIUrl":"https://doi.org/10.1126/sciadv.adq0987","url":null,"abstract":"The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the Sox2 gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites. Strikingly, enhancer mobility becomes constrained on transcriptional firing, homogenizing its dynamics with the gene promoter, suggestive of their cotranscriptional sharing of a nuclear microenvironment. Furthermore, we find transcription and loop extrusion to be antagonistic processes constraining regulatory loci. These findings indicate that modulating chromatin mobility can be an additional, underestimated means for effective gene regulation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820582","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

Light modulates glucose and lipid homeostasis via the sympathetic nervous system.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adp3284

Xiangning Chen, Eugene Lin, Mozhan M Haghighatian, Logan Wallace Shepard, Samer Hattar, Rejji Kuruvilla, Haiqing Zhao

{"title":"Light modulates glucose and lipid homeostasis via the sympathetic nervous system.","authors":"Xiangning Chen, Eugene Lin, Mozhan M Haghighatian, Logan Wallace Shepard, Samer Hattar, Rejji Kuruvilla, Haiqing Zhao","doi":"10.1126/sciadv.adp3284","DOIUrl":"10.1126/sciadv.adp3284","url":null,"abstract":"Light is an important environmental factor for vision and for diverse physiological and psychological functions. Light can also modulate glucose metabolism. Here, we show that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption. Light deprivation from birth elicits insulin hypersecretion, glucagon hyposecretion, lower gluconeogenesis, and reduced lipolysis by 6 to 8 weeks in male, but not female, mice. These metabolic defects are consistent with blunted sympathetic activity, and indeed, sympathetic responses to a cold stimulus are substantially attenuated in dark-reared mice. Further, long-term dark rearing leads to body weight gain, insulin resistance, and glucose intolerance. Notably, metabolic dysfunction can be partially alleviated by 5 weeks exposure to a regular light-dark cycle. These studies provide insight into circadian-independent mechanisms by which light directly influences whole-body physiology and better understanding of metabolic disorders linked to aberrant environmental light conditions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eadp3284"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Architecture and functional regulation of a plant PSII-LHCII megacomplex

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq9967

Jianyu Shan, Dariusz M. Niedzwiedzki, Rupal S. Tomar, Zhenfeng Liu, Haijun Liu

{"title":"Architecture and functional regulation of a plant PSII-LHCII megacomplex","authors":"Jianyu Shan, Dariusz M. Niedzwiedzki, Rupal S. Tomar, Zhenfeng Liu, Haijun Liu","doi":"10.1126/sciadv.adq9967","DOIUrl":"https://doi.org/10.1126/sciadv.adq9967","url":null,"abstract":"Photosystem II (PSII) splits water in oxygenic photosynthesis on Earth. The structure and function of the C 4 S 4 M 2 -type PSII-LHCII (light-harvesting complex II) megacomplexes from the wild-type and PsbR-deletion mutant plants are studied through electron microscopy (EM), structural mass spectrometry, and ultrafast fluorescence spectroscopy [time-resolved fluorescence (TRF)]. The cryo-EM structure of a type I C 4 S 4 M 2 megacomplex demonstrates that the three domains of PsbR bind to the stromal side of D1, D2, and CP43; associate with the single transmembrane helix of the redox active Cyt b 559 ; and stabilize the luminal extrinsic PsbP, respectively. This megacomplex, with PsbR and PsbY centered around the narrow interface between two dimeric PSII cores, provides the supramolecular structural basis that regulates the plastoquinone occupancy in Q B site, excitation energy transfer, and oxygen evolution. PSII-LHCII megacomplexes (types I and II) and LHC aggregation levels in Arabidopsis psbR mutant were also interrogated and compared to wild-type plants through EM and picosecond TRF.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820572","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

Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adt1670

Yohan Santin, Mattia Chiesa, Amélie Alfonso, Yosra Doghri, Ryeonshi Kang, Fraha Haidar, Pilar Oreja-Fuentes, Occiane Fousset, Rana Zahreddine, Mégane Guardia, Lucas Lemmel, Mara Rigamonti, Giorgio Rosati, Cédrick Florian, Sébastien Gauzin, Sophie Guyonnet, Yves Rolland, Philipe de Souto Barreto, Bruno Vellas, Bruno Guiard, Angelo Parini

{"title":"Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging","authors":"Yohan Santin, Mattia Chiesa, Amélie Alfonso, Yosra Doghri, Ryeonshi Kang, Fraha Haidar, Pilar Oreja-Fuentes, Occiane Fousset, Rana Zahreddine, Mégane Guardia, Lucas Lemmel, Mara Rigamonti, Giorgio Rosati, Cédrick Florian, Sébastien Gauzin, Sophie Guyonnet, Yves Rolland, Philipe de Souto Barreto, Bruno Vellas, Bruno Guiard, Angelo Parini","doi":"10.1126/sciadv.adt1670","DOIUrl":"https://doi.org/10.1126/sciadv.adt1670","url":null,"abstract":"Biological age, which reflects the physiological state of an individual, offers a better predictive value than chronological age for age-related diseases and mortality. Nonetheless, determining accurate functional features of biological age remains challenging due to the multifactorial nature of aging. Here, we established a unique mouse cohort comprising 1576 male and female outbred SWISS mice subjected or not to high-fat, high-sucrose diet to investigate multiorgan/system biological aging throughout adulthood. Comprehensive functional and biological phenotyping at ages of 6, 12, 18, and 24 months revealed notable sex-specific disparities in longitudinal locomotion patterns and multifunctional aging parameters. Topological data analysis enabled the identification of functionally similar mouse clusters irrespective of chronological age. Moreover, our study pinpointed critical functional markers of biological aging such as muscle function, anxiety characteristics, urinary patterns, reticulocyte maturation, cardiac remodeling and function, and metabolic alterations, underscoring muscle function as an early indicator of biological age in male mice.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"29 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820581","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

From oxide epitaxy to freestanding membranes: Opportunities and challenges.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adq8561

Sooho Choo, Shivasheesh Varshney, Huan Liu, Shivam Sharma, Richard D James, Bharat Jalan

引用次数: 0