Science Advances最新文献

{"title":"Multidisciplinary evidence for synchroneity between Ontong Java Nui volcanism and early Aptian oceanic anoxic event 1a","authors":"Hironao Matsumoto,&nbsp;Kotaro Shirai,&nbsp;Akira Ishikawa,&nbsp;Naohiko Ohkouchi,&nbsp;Nanako O. Ogawa,&nbsp;Maria Luisa G. Tejada,&nbsp;Atsushi Ando,&nbsp;Junichiro Kuroda,&nbsp;Katsuhiko Suzuki","doi":"","DOIUrl":"","url":null,"abstract":"<div >The volcanic episodes forming Ontong Java Nui (OJN) likely caused late Barremian to mid-Aptian paleoenvironmental perturbations, the most substantial of which was early Aptian oceanic anoxic event (OAE) 1a (120 million years ago). However, recent estimates on younger OJN eruption ages cast doubt on the link between OJN volcanism and OAE1a. Here, we further demonstrate the synchroneity between OJN volcanism and OAE1a by refining the chronology of Pacific volcanogenic sedimentary records on Magellan Rise, nearby OJN, with detailed osmium and carbon isotopic stratigraphy. Our geochemical data reveal that a thick tuffaceous interval at this site was deposited during OAE1a. Furthermore, multisite compilation of osmium isotopes, Pacific volcanic ash beds, and paleontological data just above OJN basalts illustrate that explosive OJN eruptions spanned ~5 million years, peaking around OAE1a. Their synchroneity strongly indicates that OJN volcanism most likely caused OAE1a and relevant late Barremian to mid-Aptian environmental perturbations.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt0204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513963","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}

{"title":"When the wild things are: Defining mammalian diel activity and plasticity","authors":"Kadambari Devarajan,&nbsp;Mason Fidino,&nbsp;Zach J. Farris,&nbsp;Solny A. Adalsteinsson,&nbsp;Gabriel Andrade-Ponce,&nbsp;Julia L. Angstmann,&nbsp;Whitney Anthonysamy,&nbsp;Jesica Aquino,&nbsp;Addisu Asefa,&nbsp;Belen Avila,&nbsp;Larissa L. Bailey,&nbsp;Lyandra Maria de Sousa Barbosa,&nbsp;Marcela de Frias Barreto,&nbsp;Owain Barton,&nbsp;Chloe E. Bates,&nbsp;Mayara Guimarães Beltrão,&nbsp;Tori Bird,&nbsp;Elizabeth G. Biro,&nbsp;Francesco Bisi,&nbsp;Daniel Bohórquez,&nbsp;Mark Boyce,&nbsp;Justin S. Brashares,&nbsp;Grace Bullington,&nbsp;Phoebe Burns,&nbsp;Jessica Burr,&nbsp;Andrew R. Butler,&nbsp;Kendall L. Calhoun,&nbsp;Tien Trung Cao,&nbsp;Natalia Casado,&nbsp;Juan Camilo Cepeda-Duque,&nbsp;Jonathon D. Cepek,&nbsp;Adriano Garcia Chiarello,&nbsp;Merri Collins,&nbsp;Pedro Cordeiro-Estrela,&nbsp;Sebastian Costa,&nbsp;Giacomo Cremonesi,&nbsp;Bogdan Cristescu,&nbsp;Paula Cruz,&nbsp;Anna Carolina Figueiredo de Albuquerque,&nbsp;Carlos De Angelo,&nbsp;Cláudia Bueno de Campos,&nbsp;Liana Mara Mendes de Sena,&nbsp;Mario Di Bitetti,&nbsp;Douglas de Matos Dias,&nbsp;Duane Diefenbach,&nbsp;Tim S. Doherty,&nbsp;Thais P. dos Santos,&nbsp;Gabriela Teixeira Duarte,&nbsp;Timothy M. Eppley,&nbsp;John Erb,&nbsp;Carolina Franco Esteves,&nbsp;Bryn Evans,&nbsp;Maria L. M. Falcão,&nbsp;Hugo Fernandes-Ferreira,&nbsp;John R. Fieberg,&nbsp;Luiz Carlos Firmino de Souza Filho,&nbsp;Jason Fisher,&nbsp;Marie-Josee Fortin,&nbsp;George A. Gale,&nbsp;Travis Gallo,&nbsp;Laken S. Ganoe,&nbsp;Rony Garcia-Anleu,&nbsp;Kaitlyn M. Gaynor,&nbsp;Tiziana A. Gelmi-Candusso,&nbsp;Phillys N. Gichuru,&nbsp;Quimey Gomez,&nbsp;Austin M. Green,&nbsp;Luiza Neves Guimarães,&nbsp;Jeffrey D. Haight,&nbsp;Lavendar R. Harris,&nbsp;Zachary D. Hawn,&nbsp;Jordan Heiman,&nbsp;Huy Quoc Hoang,&nbsp;Sarah Huebner,&nbsp;Fabiola Iannarilli,&nbsp;María Eugenia Iezzi,&nbsp;Jacob S. Ivan,&nbsp;Kodi J. Jaspers,&nbsp;Mark J. Jordan,&nbsp;Jason Kamilar,&nbsp;Mamadou Kane,&nbsp;Mohammad Hosein Karimi,&nbsp;Marcella Kelly,&nbsp;Michel T. Kohl,&nbsp;William P. Kuvlesky Jr.,&nbsp;Andrew Ladle,&nbsp;Rachel N. Larson,&nbsp;Quy Tan Le,&nbsp;Duy Le,&nbsp;Van Son Le,&nbsp;Elizabeth W. Lehrer,&nbsp;Patrick E. Lendrum,&nbsp;Jesse Lewis,&nbsp;Andrés Link,&nbsp;Diego J. Lizcano,&nbsp;Jason V. Lombardi,&nbsp;Robert Long,&nbsp;Eva López-Tello,&nbsp;Camile Lugarini,&nbsp;David Lugo,&nbsp;Paula MacKay,&nbsp;Maria Madadi,&nbsp;Rodolfo Assis Magalhães,&nbsp;Seth B. Magle,&nbsp;Ludmila Hufnagel Regis Diniz Maia,&nbsp;Salvador Mandujano,&nbsp;Taisiia Marchenkova,&nbsp;Paulo Henrique Marinho,&nbsp;Laurie Marker,&nbsp;Julia Martinez Pardo,&nbsp;Adriano Martinoli,&nbsp;Rodrigo Lima Massara,&nbsp;Juliana Masseloux,&nbsp;Dina Matiukhina,&nbsp;Amy Mayer,&nbsp;Luis Mazariegos,&nbsp;Maureen R. McClung,&nbsp;Alex McInturff,&nbsp;Darby McPhail,&nbsp;Amy Mertl,&nbsp;Christopher R. Middaugh,&nbsp;David Miller,&nbsp;David Mills,&nbsp;Dale Miquelle,&nbsp;Vivianna Miritis,&nbsp;Remington J. Moll,&nbsp;Péter Molnár,&nbsp;Robert A. Montgomery,&nbsp;Toni Lyn Morelli,&nbsp;Alessio Mortelliti,&nbsp;Rachael I. Mueller,&nbsp;Anna S. Mukhacheva,&nbsp;Kayleigh Mullen,&nbsp;Asia Murphy,&nbsp;Vance Nepomuceno,&nbsp;Dusit Ngoprasert,&nbsp;An Nguyen,&nbsp;Thanh Van Nguyen,&nbsp;Van Thai Nguyen,&nbsp;Hoa Anh Nguyen Quang,&nbsp;Rob Nipko,&nbsp;Ana Clarissa Costa Nobre,&nbsp;Joseph Northrup,&nbsp;Megan A. Owen,&nbsp;Adriano Pereira Paglia,&nbsp;Meredith S. Palmer,&nbsp;Gabriela Palomo-Munoz,&nbsp;Lain E. Pardo,&nbsp;Chrystina Parks,&nbsp;Ana Maria de Oliveira Paschoal,&nbsp;Brent Patterson,&nbsp;Agustin Paviolo,&nbsp;Liba Pejchar,&nbsp;Mary E. Pendergast,&nbsp;Humberto L. Perotto-Baldivieso,&nbsp;Timofei Petrov,&nbsp;Mairi K. P. Poisson,&nbsp;Daiana Jeronimo Polli,&nbsp;Morteza Pourmirzai,&nbsp;Alexander Reebin,&nbsp;Katie R. Remine,&nbsp;Lindsey Rich,&nbsp;Christopher S. Richardson,&nbsp;Facundo Robino,&nbsp;Daniel G. Rocha,&nbsp;Fabiana Lopes Rocha,&nbsp;Flávio Henrique Guimarães Rodrigues,&nbsp;Adam T. Rohnke,&nbsp;Travis J. Ryan,&nbsp;Carmen M. Salsbury,&nbsp;Heather A. Sander,&nbsp;Nadia Maria da Cruz Santos-Cavalcante,&nbsp;Cagan H. Sekercioglu,&nbsp;Ivan Seryodkin,&nbsp;Dede Hendra Setiawan,&nbsp;Shabnam Shadloo,&nbsp;Mahsa Shahhosseini,&nbsp;Graeme Shannon,&nbsp;Catherine J. Shier,&nbsp;G. Bradley Smith,&nbsp;Tom Snyder,&nbsp;Rahel Sollmann,&nbsp;Kimberly L. Sparks,&nbsp;Kriangsak Sribuarod,&nbsp;Colleen C. St. Clair,&nbsp;Theodore Stankowich,&nbsp;Robert Steinmetz,&nbsp;Cassondra J. Stevenson,&nbsp;Sunarto Sunarto,&nbsp;Thilina D. Surasinghe,&nbsp;Svetlana V. Sutyrina,&nbsp;Ronald R. Swaisgood,&nbsp;Atie Taktehrani,&nbsp;Kanchan Thapa,&nbsp;Matthew Thorton,&nbsp;Andrew Tilker,&nbsp;Mathias W. Tobler,&nbsp;Van Bang Tran,&nbsp;Jody Tucker,&nbsp;Russell C. Van Horn,&nbsp;Juan S. Vargas-Soto,&nbsp;Karen L. Velásquez-C,&nbsp;Jan Venter,&nbsp;Eduardo M. Venticinque,&nbsp;Stijn Verschueren,&nbsp;Erin Wampole,&nbsp;Darcy J Watchorn,&nbsp;Oliver R. Wearn,&nbsp;Katherine C.B. Weiss,&nbsp;Alejandro Welschen,&nbsp;Febri Anggriawan Widodo,&nbsp;Jacque Williamson,&nbsp;Andreas Wilting,&nbsp;George Wittemyer,&nbsp;Arturo Zavaleta,&nbsp;Amanda J. Zellmer,&nbsp;Brian D. Gerber","doi":"","DOIUrl":"","url":null,"abstract":"<div >Circadian rhythms are a mechanism by which species adapt to environmental variability and fundamental to understanding species behavior. However, we lack data and a standardized framework to accurately assess and compare temporal activity for species during rapid ecological change. Through a global network representing 38 countries, we leveraged 8.9 million mammalian observations to create a library of 14,587 standardized diel activity estimates for 445 species. We found that less than half the species’ estimates were in agreement with diel classifications from the reference literature and that species commonly used more than one diel classification. Species diel activity was highly plastic when exposed to anthropogenic change. Furthermore, body size and distributional extent were strongly associated with whether a species is diurnal or nocturnal. Our findings provide essential knowledge of species behavior in an era of rapid global change and suggest the need for a new, quantitative framework that defines diel activity logically and consistently while capturing species plasticity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado3843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513970","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}

{"title":"Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant","authors":"L. Carissa Aurelia,&nbsp;Ruth A. Purcell,&nbsp;Robert M. Theisen,&nbsp;Andrew Kelly,&nbsp;Robyn Esterbauer,&nbsp;Pradhipa Ramanathan,&nbsp;Wen Shi Lee,&nbsp;Bruce D. Wines,&nbsp;P. Mark Hogarth,&nbsp;Jennifer A. Juno,&nbsp;Lilith F. Allen,&nbsp;Katherine A. Bond,&nbsp;Deborah A. Williamson,&nbsp;Janine M. Trevillyan,&nbsp;Jason A. Trubiano,&nbsp;Thi HO Nguyen,&nbsp;Katherine Kedzierska,&nbsp;Adam K. Wheatley,&nbsp;Stephen J. Kent,&nbsp;Kelly B. Arnold,&nbsp;Kevin John Selva,&nbsp;Amy W. Chung","doi":"","DOIUrl":"","url":null,"abstract":"<div >Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity. However, in individuals with lower total spike-specific IgG, IgG4 acted in synergy with other IgG subclasses to improve FcγRI and FcγRIIa binding and consequently antibody-dependent cellular phagocytosis. Furthermore, this trend was more pronounced with more recent SARS-CoV-2 variants where vaccination induced comparably lower total spike-specific titers. These observations were further confirmed by in silico modeling where antibody subclass concentrations and FcγR polymorphisms were modulated. Collectively, we illustrate that the impact of elevated IgG4 titers upon Fc functions is dependent on multiple interconnected antibody and antigen factors, which should be taken into consideration when dissecting the mechanisms driving an effective Fc-mediated response following vaccination.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads1482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513976","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}

{"title":"Anthropogenic intensification of Arctic anticyclonic circulation","authors":"Zhongfang Liu,&nbsp;Camille Risi,&nbsp;Francis Codron,&nbsp;Guillaume Gastineau,&nbsp;Xiaohe Huan,&nbsp;Haimao Lan,&nbsp;Wanling Xu,&nbsp;Gabriel J. Bowen","doi":"","DOIUrl":"","url":null,"abstract":"<div >The past four decades have witnessed a strengthening of the winter anticyclonic circulation over the Barents-Kara Sea (BKS), a change that has contributed substantially to amplified local warming and sea ice loss, as well as to Eurasian cooling. However, the cause of this trend in the BKS atmospheric circulation remains unknown. Here we show that anthropogenic greenhouse gases are the primary driver of the strengthening of the BKS anticyclonic circulation, with anthropogenic aerosols playing a secondary role, both together accounting for about 86% of the observed circulation trend. Both forcings induce an amplified BKS low-tropospheric warming through coupling with strong sea ice loss. This amplified warming raises geopotential height aloft through thermal expansion, causing an anomalous anticyclonic anomaly, which in turn enhances warming and sea ice loss, forming a positive feedback loop. Our work provides a theoretical framework for understanding Arctic atmospheric circulation responses to anthropogenic warming and may have implications for climate and environment in the Arctic and beyond.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads4508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513948","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}

{"title":"Mining coral-derived terpene synthases and mechanistic studies of the coral biflorane synthase","authors":"Bao Chen,&nbsp;Jingjing Mao,&nbsp;Kangwei Xu,&nbsp;Lijun Liu,&nbsp;Wei Lin,&nbsp;Yue-Wei Guo,&nbsp;Ruibo Wu,&nbsp;Chengyuan Wang,&nbsp;Baofu Xu","doi":"","DOIUrl":"","url":null,"abstract":"<div >Biflorane diterpenoids are unique natural products often seen in marine animals. Recent studies have reported a small number of biflorane synthases. However, the catalytic mechanism and structural basis for biflorane formation remain unclear. To address these issues, we conducted genome mining of terpene synthases from the sea whip coral <i>Paramuricea clavata</i>, resulting in the discovery of a biflorane synthase <i>Pc</i>TS1. We performed a series of isotope labeling, crystallography, quantum mechanics/molecular mechanics calculations, and mutagenesis studies toward <i>Pc</i>TS1 to investigate the mechanism. Isotopic labeling studies, together with calculations, elucidate a cascade of 1,10-cyclization, 1,3-hydride shift, 1,6-cyclization, 1,2-hydride shift, 2,6-cyclization, cyclopropane ring opening, and deprotonation by the generated pyrophosphate, forming the biflorane scaffold. Crystallography, quantum mechanics/molecular mechanics, and mutagenesis studies confirmed the cascade and produced different terpene scaffolds. Our work demonstrated the mechanism of marine biflorane formation, elucidated the second crystal structure of a coral terpene synthase, and realized the terpene skeleton expansion.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adv0805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513967","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}

{"title":"The synaptonemal complex aligns meiotic chromosomes by wetting","authors":"Spencer G. Gordon,&nbsp;Alyssa A. Rodriguez,&nbsp;Yajie Gu,&nbsp;Kevin D. Corbett,&nbsp;Chiu Fan Lee,&nbsp;Ofer Rog","doi":"","DOIUrl":"","url":null,"abstract":"<div >During meiosis, the parental chromosomes are drawn together to enable exchange of genetic information. Chromosomes are aligned through the assembly of a conserved interface, the synaptonemal complex, composed of a central region that forms between two parallel chromosomal backbones called axes. Here, we identify the axis-central region interface in <i>C. elegans</i>, containing a conserved positive patch on the axis component HIM-3 and the negative C terminus of the central region protein SYP-5. Crucially, the canonical ultrastructure of the synaptonemal complex is altered upon weakening this interface using charge-reversal mutations. We developed a thermodynamic model that recapitulates our experimental observations, indicating that the liquid-like central region can assemble by wetting the axes without active energy consumption. More broadly, our data show that condensation drives tightly regulated nuclear reorganization during sexual reproduction.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt5675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513968","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}

{"title":"Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer","authors":"Seok-Young Kim,&nbsp;Tamar A. E. de Weert,&nbsp;Marijn Vermeulen,&nbsp;Femke Ringnalda,&nbsp;Lennart Kester,&nbsp;Jozsef Zsiros,&nbsp;Selma Eising,&nbsp;Jan J. Molenaar,&nbsp;Karin Sanders,&nbsp;Marc van de Wetering,&nbsp;Hans Clevers","doi":"","DOIUrl":"","url":null,"abstract":"<div >Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent and young adult patients. Now, there is no standard-of-care treatment for these patients. Reliable models that represent this disease and can be used for translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from tumor lesions of three patients with SCCOHT. The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC₅₀ of 35 nanomolars. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq1724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513974","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}

{"title":"Modulation of blood-tumor barrier transcriptional programs improves intratumoral drug delivery and potentiates chemotherapy in GBM","authors":"Jorge L. Jimenez-Macias,&nbsp;Philippa Vaughn-Beaucaire,&nbsp;Ayush Bharati,&nbsp;Zheyun Xu,&nbsp;Megan Forrest,&nbsp;Jason Hong,&nbsp;Michael Sun,&nbsp;Andrea Schmidt,&nbsp;Jasmine Clark,&nbsp;William Hawkins,&nbsp;Noe Mercado,&nbsp;Jacqueline Real,&nbsp;Kelsey Huntington,&nbsp;Mykola Zdioruk,&nbsp;Michal O. Nowicki,&nbsp;Choi-Fong Cho,&nbsp;Bin Wu,&nbsp;Weiyi Li,&nbsp;Theresa Logan,&nbsp;Katherine E. Manz,&nbsp;Kurt D. Pennell,&nbsp;Bogdan I. Fedeles,&nbsp;Paul Bertone,&nbsp;Michael Punsoni,&nbsp;Alexander S. Brodsky,&nbsp;Sean E. Lawler","doi":"","DOIUrl":"","url":null,"abstract":"<div >Efficient drug delivery to glioblastoma (GBM) is a major obstacle as the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) prevent passage of the majority of chemotherapies into the brain. Here, we identified a transcriptional 12-gene signature associated with the BTB in GBM. We identified CDH5 as a core molecule in this set and confirmed its expression in GBM vasculature using transcriptomics and immunostaining of patient specimens. The indirubin-derivative, 6-bromoindirubin acetoxime (BIA), down-regulates CDH5 and other BTB signature genes, causing endothelial barrier disruption in vitro and in murine GBM xenograft models. Treatment with BIA increased intratumoral cisplatin accumulation and potentiated DNA damage by targeting DNA repair pathways. Last, using an injectable BIA nanoparticle formulation, PPRX-1701, we significantly improved cisplatin efficacy in murine GBM. Our work reveals potential targets of the BTB and the bifunctional properties of BIA as a BTB modulator and a potentiator of chemotherapy, supporting its further development.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr1481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513975","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}

{"title":"Correlated nanoimaging of structure and dynamics of cation-polaron coupling in hybrid perovskites","authors":"Roland Wilcken,&nbsp;Branden L. Esses,&nbsp;Rachith S. Nithyananda Kumar,&nbsp;Lauren A. Hurley,&nbsp;Sean E. Shaheen,&nbsp;Markus B. Raschke","doi":"","DOIUrl":"","url":null,"abstract":"<div >Hybrid organic-inorganic perovskites exhibit high photovoltaic performance and other novel photonic functions. While polaron formation is believed to facilitate efficient carrier transport, the elementary processes of the underlying electron-lattice coupling are yet poorly understood because of the multiscale chemical and structural heterogeneities. Here, we resolve in combined ground- and excited-state spatiospectral ultrafast nanoimaging how structural characteristics are related to both molecular cation and polaron dynamics. We use the observed nanoscale spatial variations of the formamidinium (FA) cation transient vibrational blue shifts as a local probe of the nonlocal polaron-cation coupling. From the correlation with nanomovies of the polaron dynamics, we then infer how a softer more polarizable lattice supports stable polarons and longer-lived residual carriers. This, together with a relative intragrain homogeneity in contrast to high intergrain heterogeneity, suggests pathways for improved synthesis and device engineering, and that perovskite photonics performance is still far from any fundamental limits.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads3706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513934","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}

{"title":"An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking","authors":"Riley Merkel,&nbsp;Nicole S. Hernandez,&nbsp;Vanessa Weir,&nbsp;Yafang Zhang,&nbsp;Antonia Caffrey,&nbsp;Matthew T. Rich,&nbsp;Richard C. Crist,&nbsp;Benjamin C. Reiner,&nbsp;Heath D. Schmidt","doi":"","DOIUrl":"","url":null,"abstract":"<div >Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate cocaine seeking. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1–producing neurons in the nucleus tractus solitarius that project to the ventral tegmental area (VTA) decreased cocaine seeking. Single-nuclei transcriptomics and FISH studies revealed that GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a functional role of GABAergic GLP-1R–expressing midbrain neurons in drug seeking.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr5051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513945","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}