Science Advances最新文献

On the analysis of metabolite quantitative trait loci: Impact of different data transformations and study designs

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adp4532

Sanghun Lee, Rachel S. Kelly, Kevin M. Mendez, Dmitry Prokopenko, Georg Hahn, Sharon M. Lutz, Juan C. Celedón, Clary B. Clish, Scott T. Weiss, Christoph Lange, Jessica A. Lasky-Su, Julian Hecker, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

{"title":"On the analysis of metabolite quantitative trait loci: Impact of different data transformations and study designs","authors":"Sanghun Lee, Rachel S. Kelly, Kevin M. Mendez, Dmitry Prokopenko, Georg Hahn, Sharon M. Lutz, Juan C. Celedón, Clary B. Clish, Scott T. Weiss, Christoph Lange, Jessica A. Lasky-Su, Julian Hecker, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium","doi":"10.1126/sciadv.adp4532","DOIUrl":"10.1126/sciadv.adp4532","url":null,"abstract":"<div >Metabolomic genome-wide association studies (mGWASs), or metabolomic quantitative trait locus (metQTL) analyses, are gaining growing attention. However, robust methods and analysis guidelines, vital to address the complexity of metabolomic data, remain to be established. Here, we use whole-genome sequencing and metabolomic data from two independent studies to compare different approaches. We adopted three popular data transformation methods for metabolite levels—(i) log<sub>10</sub> transformation, (ii) rank inverse normal transformation, and (iii) a fully adjusted two-step procedure—and compared population-based versus family-based analysis approaches. For validation, we performed permutation-based testing, Huber regression, and independent replication analysis. Simulation studies were used to illustrate the observed differences between data transformations. We demonstrate the advantages and limitations of popular analytic strategies used in mGWASs where especially low-frequency variants in combination with a skewed metabolite measurement distribution can lead to potentially false-positive metQTL findings. We recommend the rank inverse normal transformation or robust test statistics such as in family-based association tests as reliable approaches for mGWASs.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp4532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822339","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

Evidence for crustal brines and deep fluid infiltration in an oceanic transform fault

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adu3661

Christine Chesley, Rob Evans, Jessica M. Warren, Andrew C. Gase, Jacob Perez, Christopher Armerding, Hannah Brewer, Paige Koenig, Eric Attias, Bailey L. Fluegel, Jae-Deok Kim, Natalie Hummel, Katherine Enright, Emilia Topp-Johnson, Margaret S. Boettcher

{"title":"Evidence for crustal brines and deep fluid infiltration in an oceanic transform fault","authors":"Christine Chesley, Rob Evans, Jessica M. Warren, Andrew C. Gase, Jacob Perez, Christopher Armerding, Hannah Brewer, Paige Koenig, Eric Attias, Bailey L. Fluegel, Jae-Deok Kim, Natalie Hummel, Katherine Enright, Emilia Topp-Johnson, Margaret S. Boettcher","doi":"10.1126/sciadv.adu3661","DOIUrl":"10.1126/sciadv.adu3661","url":null,"abstract":"<div >Although oceanic transform faults (OTFs) are ubiquitous plate boundaries, the geological processes occurring along these systems remain underexplored. The Gofar OTF of the East Pacific Rise has gained attention due to its predictable, yet enigmatic, earthquake cycle. Here, we present results from the first ever controlled-source electromagnetic survey of an OTF, which sampled Gofar. We find that the fault is characterized by a subvertical conductor, which extends into the lower crust and thus implies deep fluid penetration. We also image subhorizontal crustal conductors distributed asymmetrically about the fault. We interpret these subhorizontal anomalies as crustal brines, and we suggest that the high permeability of the fault combined with the influence of melt in the transform domain can promote hydrothermal circulation and brine condensation at OTFs.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu3661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822341","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

Diffusion power spectra as a window into dynamic materials architecture

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adt6144

Sophia N. Fricke, Mia Salgado, Shira Haber, Jeremy Demarteau, Mutian Hua, Ah-Young Song, Brett A. Helms, Jeffrey A. Reimer

{"title":"Diffusion power spectra as a window into dynamic materials architecture","authors":"Sophia N. Fricke, Mia Salgado, Shira Haber, Jeremy Demarteau, Mutian Hua, Ah-Young Song, Brett A. Helms, Jeffrey A. Reimer","doi":"10.1126/sciadv.adt6144","DOIUrl":"10.1126/sciadv.adt6144","url":null,"abstract":"<div >Chemical recycling of commodity and specialty polymers presents a multifaceted challenge for industrial societies. On one hand, macromolecular architectures must be engineered to yield durable products that, on the other hand, rapidly deconstruct to recyclable monomers under pre-determined conditions. Polymer deconstruction is a chemical process that requires deep understanding of molecular reactivity in heterogeneous media, where porous material architectures evolve in both space and time. To build this understanding, we develop herein experimental and analytical methods describing sets of diffusive eigenmodes that exist within time-varying, non-Euclidean boundary conditions, a situation commonly encountered in the reactive deconstruction of polymers where chain fragments splay, alter their local dynamics, and evolve in their confinement of reacting media. Diffusion power spectra, discerned experimentally by NMR, yield polymer and solvent frequency-domain velocity autocorrelation functions that are analyzed in the context of physical models for chemical reactions parameterized with fractal mathematics. The results connect local motion in polymers to chemical reactivity during acidolysis of circular elastomers.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt6144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822342","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

Confirmation of Breslow’s hypothesis: A carbene stable in liquid water

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adr9681

Varun Tej Raviprolu, Aaron Gregory, Isaac Banda, Scott G. McArthur, Sarah E. McArthur, William A. Goddard III, Charles B. Musgrave III, Vincent Lavallo

引用次数: 0

A dual-mechanism luminescent antibiotic for bacterial infection identification and eradication

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adp9448

Guobin Qi, Xianglong Liu, Hao Li, Yunyun Qian, Can Liu, Jiahao Zhuang, Leilei Shi, Bin Liu

引用次数: 0

Radiative cooling induced coherent maser emission in relativistic plasmas

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adt8912

Pablo J. Bilbao, Thales Silva, Luís O. Silva

{"title":"Radiative cooling induced coherent maser emission in relativistic plasmas","authors":"Pablo J. Bilbao, Thales Silva, Luís O. Silva","doi":"10.1126/sciadv.adt8912","DOIUrl":"10.1126/sciadv.adt8912","url":null,"abstract":"<div >Relativistic plasmas in strong electromagnetic fields exhibit distinct properties compared to classical plasmas. In astrophysical environments, such as neutron stars, white dwarfs, active galactic nuclei, and shocks, relativistic plasmas are pervasive and are expected to play a crucial role in the dynamics of these systems. Despite their significance, experimental and theoretical studies of these plasmas have been limited. Here, we present the first ab initio high-resolution kinetic simulations of relativistic plasmas undergoing synchrotron cooling in a highly magnetized medium. Our results demonstrate that these plasmas spontaneously generate coherent linearly polarized radiation in a wide range of parameters via the electron cyclotron maser instability, with radiative losses altering the saturation mechanism. Thus, the plasma continuously amplify coherent radiation for substantially longer durations of time. These findings highlight fundamental differences in the behavior of relativistic plasmas in strongly magnetized environments and align with astronomical phenomena, such as pulsar emission and fast radio bursts.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt8912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822366","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

The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adt6159

Yu Zhang, Jie Bai, Bo Xiong

{"title":"The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes","authors":"Yu Zhang, Jie Bai, Bo Xiong","doi":"10.1126/sciadv.adt6159","DOIUrl":"10.1126/sciadv.adt6159","url":null,"abstract":"<div >Chromosome cohesion mediated by cohesin complex and its associated proteins is required for accurate chromosome segregation and genomic stability in mitosis. However, because of the distinct operation mechanisms, many proteins might exert different functions during meiosis in germ cells. Here, we document that cohesin-associated protein precocious dissociation of sisters 5A (Pds5A) plays a noncanonical role in the meiotic spindle assembly during oocyte maturation independent of its cohesion function. Pds5A distributes on the spindle fibers in oocytes at both metaphase I and metaphase II stages. Morpholino-based depletion or genetic ablation of Pds5A all lead to defects in spindle organization, chromosome euploidy and meiotic progression in oocytes and thus compromising the female fertility. Mechanistically, Pds5A recruits deubiquitinase ubiquitin-specific protease 14 to the spindle apparatus for stabilization of kinesin family member 5B, regulating the spindle elongation. Collectively, our findings unveil that cohesin-associated protein Pds5A can be used as a spindle regulator during oocyte meiosis.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt6159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822371","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

Discovery of synthetic small molecules targeting the central regulator of Salmonella pathogenicity

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adr5235

Abdelhakim Boudrioua, Joe D. Joiner, Iwan Grin, Thales Kronenberger, Vadim S. Korotkov, Wieland Steinchen, Alexander Kohler, Sophie Schminke, Julia-Christina Schulte, Michael Pietsch, Arun Naini, Simon Kalverkamp, Sven-Kevin Hotop, Travis Coyle, Claudio Piselli, Murray Coles, Katharina Rox, Matthias Marschal, Gert Bange, Antje Flieger, Antti Poso, Mark Brönstrup, Marcus D. Hartmann, Samuel Wagner

{"title":"Discovery of synthetic small molecules targeting the central regulator of Salmonella pathogenicity","authors":"Abdelhakim Boudrioua, Joe D. Joiner, Iwan Grin, Thales Kronenberger, Vadim S. Korotkov, Wieland Steinchen, Alexander Kohler, Sophie Schminke, Julia-Christina Schulte, Michael Pietsch, Arun Naini, Simon Kalverkamp, Sven-Kevin Hotop, Travis Coyle, Claudio Piselli, Murray Coles, Katharina Rox, Matthias Marschal, Gert Bange, Antje Flieger, Antti Poso, Mark Brönstrup, Marcus D. Hartmann, Samuel Wagner","doi":"10.1126/sciadv.adr5235","DOIUrl":"10.1126/sciadv.adr5235","url":null,"abstract":"<div >The enteric pathogen <i>Salmonella enterica</i> serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells and other tissues, thereby causing disease. Secretion and injection of effector proteins into host cells is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report the identification of a synthetic small molecule with drug-like properties, C26, which suppresses the secretion of effector proteins and consequently hinders bacterial invasion of eukaryotic cells. C26 binds to and inhibits HilD, the transcriptional regulator of the major secretion systems. Although sharing the same binding pocket as the previously described long-chain fatty acid ligands, C26 inhibits HilD with a unique binding mode and a distinct mechanism. We provide evidence of intramacrophage activity and present analogs with improved potency and suitability as scaffolds to develop antivirulence agents against <i>Salmonella</i> infections in humans and animals.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr5235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822352","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

Make it flow from solid to liquid: Redox-active electrofluids for intrinsically stretchable batteries

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adr9010

Mohsen Mohammadi, Saeed Mardi, Jaywant Phopase, Filippa Wentz, Jibin J. Samuel, Ujwala Ail, Magnus Berggren, Reverant Crispin, Klas Tybrandt, Aiman Rahmanudin

{"title":"Make it flow from solid to liquid: Redox-active electrofluids for intrinsically stretchable batteries","authors":"Mohsen Mohammadi, Saeed Mardi, Jaywant Phopase, Filippa Wentz, Jibin J. Samuel, Ujwala Ail, Magnus Berggren, Reverant Crispin, Klas Tybrandt, Aiman Rahmanudin","doi":"10.1126/sciadv.adr9010","DOIUrl":"10.1126/sciadv.adr9010","url":null,"abstract":"<div >High-capacity stretchable batteries are crucial for next-generation wearables to enable long-term operation and mechanical conformability with the human user. In existing stretchable battery designs, increasing the active material to yield higher capacity often leads to thicker and stiffer solid electrodes with poor mechanical properties. Here, we present a concept that transfers the physical property of a battery electrode from a conventional solid into a fluid state. The mechanical and electrochemical properties of the electrode rely on the viscosity of fluids rather than Young’s modulus of solids. Fluids conform easily into any shape with minimal force, making them intrinsically deformable. This decouples the electrochemical and mechanical property of the redox-active electrofluid, leading to higher capacities with more active material loading without stiffening the cell. The cell showed excellent capacity retention over 500 charge-discharge cycles and mechanical robustness up to 100% strain. Our work provides a technological solution for stretchable batteries that balances capacity and mechanical performance.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr9010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822303","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

Astrocytic RNA editing regulates the host immune response to alpha-synuclein

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2025-04-11 DOI: 10.1126/sciadv.adp8504

Karishma D''Sa, Minee L. Choi, Aaron Z. Wagen, Núria Setó-Salvia, Olga Kopach, James R. Evans, Margarida Rodrigues, Patricia Lopez-Garcia, Joanne Lachica, Benjamin E. Clarke, Jaijeet Singh, Ali Ghareeb, James Bayne, Melissa Grant-Peters, Sonia Garcia-Ruiz, Zhongbo Chen, Samuel Rodriques, Dilan Athauda, Emil K. Gustavsson, Sarah A. Gagliano Taliun, Christina Toomey, Regina H. Reynolds, George Young, Stephanie Strohbuecker, Thomas Warner, Dmitri A. Rusakov, Rickie Patani, Clare Bryant, David A. Klenerman, Sonia Gandhi, Mina Ryten

{"title":"Astrocytic RNA editing regulates the host immune response to alpha-synuclein","authors":"Karishma D''Sa, Minee L. Choi, Aaron Z. Wagen, Núria Setó-Salvia, Olga Kopach, James R. Evans, Margarida Rodrigues, Patricia Lopez-Garcia, Joanne Lachica, Benjamin E. Clarke, Jaijeet Singh, Ali Ghareeb, James Bayne, Melissa Grant-Peters, Sonia Garcia-Ruiz, Zhongbo Chen, Samuel Rodriques, Dilan Athauda, Emil K. Gustavsson, Sarah A. Gagliano Taliun, Christina Toomey, Regina H. Reynolds, George Young, Stephanie Strohbuecker, Thomas Warner, Dmitri A. Rusakov, Rickie Patani, Clare Bryant, David A. Klenerman, Sonia Gandhi, Mina Ryten","doi":"10.1126/sciadv.adp8504","DOIUrl":"10.1126/sciadv.adp8504","url":null,"abstract":"<div >RNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson’s disease (PD). We generated human induced pluripotent stem cell–derived astrocytes, neurons and cocultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with Toll-like receptor activation, viral responses, and cytokine secretion. This reactive state resulted in loss of neurosupportive functions and the induction of neuronal toxicity. Notably, interferon response pathways were activated leading to up-regulation and isoform switching of the RNA deaminase enzyme, ADAR1. ADAR1 mediates A-to-I RNA editing, and increases in RNA editing were observed in inflammatory pathways in cells, as well as in postmortem human PD brain. Aberrant, or dysregulated, ADAR1 responses and RNA editing may lead to sustained inflammatory reactive states in astrocytes triggered by alpha-synuclein aggregation, and this may drive the neuroinflammatory cascade in Parkinson’s.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp8504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822344","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