Science Advances

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ISSN / EISSN : 23752548 / 23752548
Total articles ≅ 3,290
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Yuan Hung Lo, Chen-Ting Liao, Jihan Zhou, Arjun Rana, Charles S. Bevis, Guan Gui, Bjoern Enders, Kevin M. Cannon, Young-Sang Yu, Richard Celestre, et al.
Science Advances, Volume 5; doi:10.1126/sciadv.aax3009

Abstract:Multimodal microscopy that combines complementary nanoscale imaging techniques is critical for extracting comprehensive chemical, structural, and functional information, particularly for heterogeneous samples. X-ray microscopy can achieve high-resolution imaging of bulk materials with chemical, magnetic, electronic, and bond orientation contrast, while electron microscopy provides atomic-scale spatial resolution with quantitative elemental composition. Here, we combine x-ray ptychography and scanning transmission x-ray spectromicroscopy with three-dimensional energy-dispersive spectroscopy and electron tomography to perform structural and chemical mapping of an Allende meteorite particle with 15-nm spatial resolution. We use textural and quantitative elemental information to infer the mineral composition and discuss potential processes that occurred before or after accretion. We anticipate that correlative x-ray and electron microscopy overcome the limitations of individual imaging modalities and open up a route to future multiscale nondestructive microscopies of complex functional materials and biological systems.
Ming Xiao, Ziying Hu, Thomas E. Gartner, Xiaozhou Yang, Weiyao Li, Arthi Jayaraman, Nathan C. Gianneschi, Matthew D. Shawkey, Ali Dhinojwala
Science Advances, Volume 5; doi:10.1126/sciadv.aax1254

Abstract:Surface segregation in binary colloidal mixtures offers a simple way to control both surface and bulk properties without affecting their bulk composition. Here, we combine experiments and coarse-grained molecular dynamics (CG-MD) simulations to delineate the effects of particle chemistry and size on surface segregation in photonic colloidal assemblies from binary mixtures of melanin and silica particles of size ratio (Dlarge/Dsmall) ranging from 1.0 to ~2.2. We find that melanin and/or smaller particles segregate at the surface of micrometer-sized colloidal assemblies (supraballs) prepared by an emulsion process. Conversely, no such surface segregation occurs in films prepared by evaporative assembly. CG-MD simulations explain the experimental observations by showing that particles with the larger contact angle (melanin) are enriched at the supraball surface regardless of the relative strength of particle-interface interactions, a result with implications for the broad understanding and design of colloidal particle assemblies.
Jin Li, Jaehun Cho, Jie Ding, Harry Charalambous, Sichuang Xue, Han Wang, Xin Li Phuah, Jie Jian, Xuejing Wang, Colin Ophus, et al.
Science Advances, Volume 5; doi:10.1126/sciadv.aaw5519

Abstract:Ceramic materials have been widely used for structural applications. However, most ceramics have rather limited plasticity at low temperatures and fracture well before the onset of plastic yielding. The brittle nature of ceramics arises from the lack of dislocation activity and the need for high stress to nucleate dislocations. Here, we have investigated the deformability of TiO2 prepared by a flash-sintering technique. Our in situ studies show that the flash-sintered TiO2 can be compressed to ~10% strain under room temperature without noticeable crack formation. The room temperature plasticity in flash-sintered TiO2 is attributed to the formation of nanoscale stacking faults and nanotwins, which may be assisted by the high-density preexisting defects and oxygen vacancies introduced by the flash-sintering process. Distinct deformation behaviors have been observed in flash-sintered TiO2 deformed at different testing temperatures, ranging from room temperature to 600°C. Potential mechanisms that may render ductile ceramic materials are discussed.
E. Bevacqua, D. Maraun, M. I. Vousdoukas, E. Voukouvalas, M. Vrac, L. Mentaschi, M. Widmann
Science Advances, Volume 5; doi:10.1126/sciadv.aaw5531

Abstract:In low-lying coastal areas, the co-occurrence of high sea level and precipitation resulting in large runoff may cause compound flooding (CF). When the two hazards interact, the resulting impact can be worse than when they occur individually. Both storm surges and heavy precipitation, as well as their interplay, are likely to change in response to global warming. Despite the CF relevance, a comprehensive hazard assessment beyond individual locations is missing, and no studies have examined CF in the future. Analyzing co-occurring high sea level and heavy precipitation in Europe, we show that the Mediterranean coasts are experiencing the highest CF probability in the present. However, future climate projections show emerging high CF probability along parts of the northern European coast. In several European regions, CF should be considered as a potential hazard aggravating the risk caused by mean sea level rise in the future.
Jiang Zhu, Christopher J. Poulsen, Jessica E. Tierney
Science Advances, Volume 5; doi:10.1126/sciadv.aax1874

Abstract:The Early Eocene, a period of elevated atmospheric CO2 (>1000 ppmv), is considered an analog for future climate. Previous modeling attempts have been unable to reproduce major features of Eocene climate indicated by proxy data without substantial modification to the model physics. Here, we present simulations using a state-of-the-art climate model forced by proxy-estimated CO2 levels that capture the extreme surface warmth and reduced latitudinal temperature gradient of the Early Eocene and the warming of the Paleocene-Eocene Thermal Maximum. Our simulations exhibit increasing equilibrium climate sensitivity with warming and suggest an Eocene sensitivity of more than 6.6°C, much greater than the present-day value (4.2°C). This higher climate sensitivity is mainly attributable to the shortwave cloud feedback, which is linked primarily to cloud microphysical processes. Our findings highlight the role of small-scale cloud processes in determining large-scale climate changes and suggest a potential increase in climate sensitivity with future warming.
Birger Schmitz, Kenneth A. Farley, Steven Goderis, Philipp R. Heck, Stig M. Bergström, Samuele Boschi, Philippe Claeys, Vinciane Debaille, Andrei Dronov, Matthias Van Ginneken, et al.
Science Advances, Volume 5; doi:10.1126/sciadv.aax4184

Abstract:The breakup of the L-chondrite parent body in the asteroid belt 466 million years (Ma) ago still delivers almost a third of all meteorites falling on Earth. Our new extraterrestrial chromite and 3He data for Ordovician sediments show that the breakup took place just at the onset of a major, eustatic sea level fall previously attributed to an Ordovician ice age. Shortly after the breakup, the flux to Earth of the most fine-grained, extraterrestrial material increased by three to four orders of magnitude. In the present stratosphere, extraterrestrial dust represents 1% of all the dust and has no climatic significance. Extraordinary amounts of dust in the entire inner solar system during >2 Ma following the L-chondrite breakup cooled Earth and triggered Ordovician icehouse conditions, sea level fall, and major faunal turnovers related to the Great Ordovician Biodiversification Event.
Emily Lorenzen, Tea Dodig-Crnković, Ilana B. Kotliar, Elisa Pin, Emilie Ceraudo, Roger D. Vaughan, Mathias Uhlèn, Thomas Huber, Jochen M. Schwenk, Thomas P. Sakmar
Science Advances, Volume 5; doi:10.1126/sciadv.aaw2778

Abstract:Receptor activity–modifying proteins (RAMPs) have been shown to modulate the functions of several G protein–coupled receptors (GPCRs), but potential direct interactions among the three known RAMPs and hundreds of GPCRs have never been investigated. Focusing mainly on the secretin-like family of GPCRs, we engineered epitope-tagged GPCRs and RAMPs, and developed a multiplexed suspension bead array (SBA) immunoassay to detect GPCR-RAMP complexes from detergent-solubilized lysates. Using 64 antibodies raised against the native proteins and 4 antibodies targeting the epitope tags, we mapped the interactions among 23 GPCRs and 3 RAMPs. We validated nearly all previously reported secretin-like GPCR-RAMP interactions, and also found previously unidentified RAMP interactions with additional secretin-like GPCRs, chemokine receptors, and orphan receptors. The results provide a complete interactome of secretin-like GPCRs with RAMPs. The SBA strategy will be useful to search for additional GPCR-RAMP complexes and other interacting membrane protein pairs in cell lines and tissues.
Jeffim N. Kuznetsov, Tristan H. Aguero, Dawn A. Owens, Stefan Kurtenbach, Matthew G. Field, Michael A. Durante, Daniel A. Rodriguez, Mary Lou King, J. William Harbour
Science Advances, Volume 5; doi:10.1126/sciadv.aax1738

Abstract:The BAP1 tumor suppressor is mutated in many human cancers such as uveal melanoma, leading to poor patient outcome. It remains unclear how BAP1 functions in normal biology or how its loss promotes cancer progression. Here, we show that Bap1 is critical for commitment to ectoderm, mesoderm, and neural crest lineages during Xenopus laevis development. Bap1 loss causes transcriptional silencing and failure of H3K27ac to accumulate at promoters of key genes regulating pluripotency-to-commitment transition, similar to findings in uveal melanoma. The Bap1-deficient phenotype can be rescued with human BAP1, by pharmacologic inhibition of histone deacetylase (HDAC) activity or by specific knockdown of Hdac4. Similarly, BAP1-deficient uveal melanoma cells are preferentially vulnerable to HDAC4 depletion. These findings show that Bap1 regulates lineage commitment through H3K27ac-mediated transcriptional activation, at least in part, by modulation of Hdac4, and they provide insights into how BAP1 loss promotes cancer progression.
Ashley Whillans, Lucía Macchia, Elizabeth Dunn
Science Advances, Volume 5; doi:10.1126/sciadv.aax2615

Abstract:How does prioritizing time or money shape major life decisions and subsequent well-being? In a preregistered longitudinal study of approximately 1000 graduating university students, respondents who valued time over money chose more intrinsically rewarding activities and were happier 1 year after graduation. These results remained significant controlling for baseline happiness and potential confounds, such as materialism and socioeconomic status, and when using alternative model specifications. These findings extend previous research by showing that the tendency to value time over money is predictive not only of daily consumer choices but also of major life decisions. In addition, this research uncovers a previously unidentified mechanism—the pursuit of intrinsically motivated activities—that underlies the previously observed association between valuing time and happiness. This work sheds new light on whether, when, and how valuing time shapes happiness.
Lei Wang, Lixiao Zhang, Li Li, Jingsheng Jiang, Zhen Zheng, Jialin Shang, Chengxiang Wang, Weilin Chen, Qichao Bao, Xiaoli Xu, et al.
Science Advances, Volume 5; doi:10.1126/sciadv.aax2277

Abstract:Disrupting the interactions between Hsp90 and Cdc37 is emerging as an alternative and specific way to regulate the Hsp90 chaperone cycle in a manner not involving adenosine triphosphatase inhibition. Here, we identified DDO-5936 as a small-molecule inhibitor of the Hsp90-Cdc37 protein-protein interaction (PPI) in colorectal cancer. DDO-5936 disrupted the Hsp90-Cdc37 PPI both in vitro and in vivo via binding to a previously unknown site on Hsp90 involving Glu47, one of the binding determinants for the Hsp90-Cdc37 PPI, leading to selective down-regulation of Hsp90 kinase clients in HCT116 cells. In addition, inhibition of Hsp90-Cdc37 complex formation by DDO-5936 resulted in a remarkable cyclin-dependent kinase 4 decrease and consequent inhibition of cell proliferation through Cdc37-dependent cell cycle arrest. Together, our results demonstrated DDO-5936 as an identified specific small-molecule inhibitor of the Hsp90-Cdc37 PPI that could be used to comprehensively investigate alternative approaches targeting Hsp90 chaperone cycles for cancer therapy.