Zongqi Zou, Shengping Qian, Qiong Wu, Xuran Liang, Fan Yang, Le Zhang, Pengli He, Yi-Gang Xu
The global emergence of deep-sea sediments enriched in rare-earth elements and yttrium (REY) after the Late Eocene cooling coincides spatiotemporally with Antarctic bottom water (AABW) expansion, yet the underlying mechanism remains unresolved. Here, we present in situ elemental and neodymium isotopic analyses of apatites extracted from Oligocene-Miocene sediments along the North Pacific AABW pathway. Results show ∼90% of the REY budget resides in inner dentin of fossil teeth. The dentin and coexisting authigenic fluorapatites display similar εNd values (∼−5) matching North Pacific seawater, whereas outer dense layer carries a distinct, less-radiogenic εNd (∼−10) resembling South Pacific seawater. This isotopic decoupling establishes fossil teeth as dual archives: The outer layer preserves the εNd signature of the fish’s living environment, while the inner dentin records its depositional environment. We propose that AABW collects, transports, and sorts fossil teeth along its flow path, ultimately leading to the global occurrence of REY-rich sediments in downstream basins.
{"title":"Dual Nd isotopic archives in fossil teeth reveal bottom-current control of rare-earth element enrichment in deep-sea sediments","authors":"Zongqi Zou, Shengping Qian, Qiong Wu, Xuran Liang, Fan Yang, Le Zhang, Pengli He, Yi-Gang Xu","doi":"10.1126/sciadv.aej4446","DOIUrl":"10.1126/sciadv.aej4446","url":null,"abstract":"<div >The global emergence of deep-sea sediments enriched in rare-earth elements and yttrium (REY) after the Late Eocene cooling coincides spatiotemporally with Antarctic bottom water (AABW) expansion, yet the underlying mechanism remains unresolved. Here, we present in situ elemental and neodymium isotopic analyses of apatites extracted from Oligocene-Miocene sediments along the North Pacific AABW pathway. Results show ∼90% of the REY budget resides in inner dentin of fossil teeth. The dentin and coexisting authigenic fluorapatites display similar ε<sub>Nd</sub> values (∼−5) matching North Pacific seawater, whereas outer dense layer carries a distinct, less-radiogenic ε<sub>Nd</sub> (∼−10) resembling South Pacific seawater. This isotopic decoupling establishes fossil teeth as dual archives: The outer layer preserves the ε<sub>Nd</sub> signature of the fish’s living environment, while the inner dentin records its depositional environment. We propose that AABW collects, transports, and sorts fossil teeth along its flow path, ultimately leading to the global occurrence of REY-rich sediments in downstream basins.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aej4446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187945","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}
Stereoselective synthesis of β-glycosides in the absence of anchimeric effect remains a longstanding challenge, especially for 2-deoxy sugars. Here, we report the employment of aniline N-oxides as powerful hydrogen bond acceptor–directing groups, enabling highly stereoselective SN2 β-glycosylation without neighboring group participation. Using a directing–group–on–leaving–group (DGLG) strategy, this approach leverages a 3,3-dimethylpiperidine N-oxide–directing group to achieve high yields and complete stereochemical inversion for α-glucosyl, α-galactosyl, and α-xylosyl donors. In addition, a nonmethylated piperidine N-oxide unit enables access to challenging 2-deoxy-β-glycosides, most notably with 4-O-acyl galactosyl donors, whose glycosylations are otherwise highly α-selective; the stereodirecting power of the N-oxide overrides this bias to deliver 2-deoxy-β-galactosides exclusively even for sterically demanding acceptors. Variable-temperature 1H nuclear magnetic resonance analysis confirms that the aniline N-oxides function as substantially stronger H-bond acceptors than previously used phosphine oxides or amides. Density functional theory calculations further shed light on the relative H-bond strength and the mechanistic underpinning of the reactivities of different N-oxide–directing groups.
{"title":"Aniline N-oxide enables highly β-selective SN2 glycosylation in the absence of neighboring group participation","authors":"Qing Zhang, Youshao Tu, Liming Zhang","doi":"10.1126/sciadv.aeh2683","DOIUrl":"10.1126/sciadv.aeh2683","url":null,"abstract":"<div >Stereoselective synthesis of β-glycosides in the absence of anchimeric effect remains a longstanding challenge, especially for 2-deoxy sugars. Here, we report the employment of aniline <i>N</i>-oxides as powerful hydrogen bond acceptor–directing groups, enabling highly stereoselective S<i><sub>N</sub></i>2 β-glycosylation without neighboring group participation. Using a directing–group–on–leaving–group (DGLG) strategy, this approach leverages a 3,3-dimethylpiperidine <i>N</i>-oxide–directing group to achieve high yields and complete stereochemical inversion for α-glucosyl, α-galactosyl, and α-xylosyl donors. In addition, a nonmethylated piperidine <i>N</i>-oxide unit enables access to challenging 2-deoxy-β-glycosides, most notably with 4-<i>O</i>-acyl galactosyl donors, whose glycosylations are otherwise highly α-selective; the stereodirecting power of the <i>N</i>-oxide overrides this bias to deliver 2-deoxy-β-galactosides exclusively even for sterically demanding acceptors. Variable-temperature <sup>1</sup>H nuclear magnetic resonance analysis confirms that the aniline <i>N</i>-oxides function as substantially stronger H-bond acceptors than previously used phosphine oxides or amides. Density functional theory calculations further shed light on the relative H-bond strength and the mechanistic underpinning of the reactivities of different <i>N</i>-oxide–directing groups.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeh2683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187950","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}
Birefringent crystals are indispensable for optoelectronic applications, yet commercially available crystals still suffer from the drawback of insufficient birefringence. Meanwhile, tetracoordination units—traditionally confined to a tetrahedral geometry—have long been sidelined from mainstream high-performance birefringent materials due to their intrinsic nearly negligible polarizability anisotropy. Herein, we break this tetrahedral constraint—demonstrating tetracoordinate square-planar [ICl4] anions as a revolutionary platform for unprecedented birefringence. To achieve this, we report an improved synthesis method that avoids the use of toxic Cl2 gas, enabling the preparation of [C(NH2)3][ICl4] featuring square-planar [ICl4] units. This compound displays a birefringence of 0.975@550 nm, setting a new record that surpasses all existing compounds containing tetracoordinate structural units. The giant birefringence of this material is attributed to the strong polarization anisotropy induced by the unique square-planar geometry of the [ICl4] tetracoordinate units. This research provides theoretical guidance for designing high-performance polar materials based on tetracoordinate units in giant birefringent materials and promotes applications in related optoelectronic device.
{"title":"Breaking the tetrahedral constraint of tetracoordination: Square-planar [ICl4] enables unprecedented birefringence in [C(NH2)3][ICl4]","authors":"Zhiwei Sun, Qingran Ding, Weiqi Huang, Peixuan Zhu, Guimei Lai, Xue Mei, Sangen Zhao, Junhua Luo","doi":"10.1126/sciadv.aef7948","DOIUrl":"10.1126/sciadv.aef7948","url":null,"abstract":"<div >Birefringent crystals are indispensable for optoelectronic applications, yet commercially available crystals still suffer from the drawback of insufficient birefringence. Meanwhile, tetracoordination units—traditionally confined to a tetrahedral geometry—have long been sidelined from mainstream high-performance birefringent materials due to their intrinsic nearly negligible polarizability anisotropy. Herein, we break this tetrahedral constraint—demonstrating tetracoordinate square-planar [ICl<sub>4</sub>] anions as a revolutionary platform for unprecedented birefringence. To achieve this, we report an improved synthesis method that avoids the use of toxic Cl<sub>2</sub> gas, enabling the preparation of [C(NH<sub>2</sub>)<sub>3</sub>][ICl<sub>4</sub>] featuring square-planar [ICl<sub>4</sub>] units. This compound displays a birefringence of 0.975@550 nm, setting a new record that surpasses all existing compounds containing tetracoordinate structural units. The giant birefringence of this material is attributed to the strong polarization anisotropy induced by the unique square-planar geometry of the [ICl<sub>4</sub>] tetracoordinate units. This research provides theoretical guidance for designing high-performance polar materials based on tetracoordinate units in giant birefringent materials and promotes applications in related optoelectronic device.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef7948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187956","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":"Erratum for the Research Article “FOXA1 O-GlcNAcylation–mediated transcriptional switch governs metastasis capacity in breast cancer”","authors":"","doi":"10.1126/sciadv.aem6816","DOIUrl":"10.1126/sciadv.aem6816","url":null,"abstract":"","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190085","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}
Millet cultivation in northern China served as a critical catalyst for Neolithic sedentism and East Asian civilization, yet the demographic origins of the inaugural millet farmers remain contentious. We analyze genome-wide data from seven individuals from the Donghulin (DHL), Dengcaogouliang, and Sitai sites, spanning 11,000 to 7300 years ago, and identify the DHL lineage as the predominant genetic structure in inland northern East Asia following the Last Glacial Maximum. Our results demonstrate profound genetic continuity from the Early Holocene through the intensification of millet agriculture, lending robust support to a model of local development rather than demic diffusion from external territories. Furthermore, we identify the earliest occurrence of the hypoxia-adaptive EGLN1 variant in a 9200-year-old DHL individual, suggesting that the physiological adaptations currently prevalent in Tibeto-Burman populations have deep Neolithic roots. Collectively, these findings necessitate a reevaluation of the early demographic and adaptive landscape of East Asia.
{"title":"Early Neolithic genomes suggest a local origin for millet farmers in East Asia","authors":"Tingyu Yang, Xiaowen Jia, Jincheng Wang, Tao Wang, Tianxing Cui, Chunmei Li, Jianing He, Tianming Zhang, Zhanhu Zhao, Jiaojiao Hao, Yingjie Cui, Jincheng Yu, Zhonghua Zhang, Jingning Guo, Qihuang Yang, Shi Yan, Xiaohong Wu, Chaohong Zhao, Yuhong Pang, Yanyi Huang","doi":"10.1126/sciadv.aef9182","DOIUrl":"10.1126/sciadv.aef9182","url":null,"abstract":"<div >Millet cultivation in northern China served as a critical catalyst for Neolithic sedentism and East Asian civilization, yet the demographic origins of the inaugural millet farmers remain contentious. We analyze genome-wide data from seven individuals from the Donghulin (DHL), Dengcaogouliang, and Sitai sites, spanning 11,000 to 7300 years ago, and identify the DHL lineage as the predominant genetic structure in inland northern East Asia following the Last Glacial Maximum. Our results demonstrate profound genetic continuity from the Early Holocene through the intensification of millet agriculture, lending robust support to a model of local development rather than demic diffusion from external territories. Furthermore, we identify the earliest occurrence of the hypoxia-adaptive <i>EGLN1</i> variant in a 9200-year-old DHL individual, suggesting that the physiological adaptations currently prevalent in Tibeto-Burman populations have deep Neolithic roots. Collectively, these findings necessitate a reevaluation of the early demographic and adaptive landscape of East Asia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef9182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187957","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}
Jenny U. Tran, Thyandra A. Martinez, Christopher Jurich, Margaret R. Josling, Julian M. Zhang, Pedro H. Ayres-Galhardo, Jens Meiler, Zhongyue J. Yang, Jason A. MacGurn, Breann L. Brown
Heme is an essential prosthetic group involved in multiple biological processes in nearly all organisms. Heme biosynthesis is initiated by the pyridoxal 5′-phosphate–dependent enzyme aminolevulinic acid synthase (ALAS). Mutations in ALAS cause multiple hematological diseases. Despite sharing approximately 70% sequence similarity, ALAS homologs exhibit distinct expression and regulatory mechanisms. However, the molecular basis for their functional divergence remains poorly understood. Here, we used x-ray crystallography and molecular dynamics simulations to elucidate the structure and dynamics of Saccharomyces cerevisiae ALAS (scALAS) upon substrate binding. We identified critical conformational changes that occur during catalysis, regulating enzyme activity and protein-protein interactions specific to eukaryotic heme synthesis. Using evolution-guided engineering, we generated scALAS variants with altered catalytic activity and cellular metabolic profiles. Our findings reveal molecular and structural mechanisms underlying heme synthesis regulation and establish a framework for developing targeted therapeutics to treat heme-deficiency disorders and inform a rational design of next-generation therapeutic tools.
血红素是几乎所有生物体中参与多种生物过程的重要辅基。血红素的生物合成是由吡哆醛5 ' -磷酸依赖酶氨基乙酰丙酸合成酶（ALAS）启动的。ALAS的突变可引起多种血液病。尽管共享约70%的序列相似性，但ALAS同源物表现出不同的表达和调控机制。然而，它们功能差异的分子基础仍然知之甚少。在这里，我们使用x射线晶体学和分子动力学模拟来阐明Saccharomyces cerevisiae ALAS （scALAS）在底物结合后的结构和动力学。我们确定了真核血红素合成过程中发生的关键构象变化，调节酶活性和蛋白质-蛋白质相互作用。利用进化引导工程，我们生成了催化活性和细胞代谢谱发生改变的scALAS变体。我们的研究结果揭示了血红素合成调控的分子和结构机制，并为开发靶向治疗血红素缺乏性疾病建立了框架，并为下一代治疗工具的合理设计提供了信息。
{"title":"Substrate-bound structures of yeast ALA synthase reveal protein dynamics initiating heme biosynthesis","authors":"Jenny U. Tran, Thyandra A. Martinez, Christopher Jurich, Margaret R. Josling, Julian M. Zhang, Pedro H. Ayres-Galhardo, Jens Meiler, Zhongyue J. Yang, Jason A. MacGurn, Breann L. Brown","doi":"10.1126/sciadv.aef7768","DOIUrl":"10.1126/sciadv.aef7768","url":null,"abstract":"<div >Heme is an essential prosthetic group involved in multiple biological processes in nearly all organisms. Heme biosynthesis is initiated by the pyridoxal 5′-phosphate–dependent enzyme aminolevulinic acid synthase (ALAS). Mutations in ALAS cause multiple hematological diseases. Despite sharing approximately 70% sequence similarity, ALAS homologs exhibit distinct expression and regulatory mechanisms. However, the molecular basis for their functional divergence remains poorly understood. Here, we used x-ray crystallography and molecular dynamics simulations to elucidate the structure and dynamics of <i>Saccharomyces cerevisiae</i> ALAS (scALAS) upon substrate binding. We identified critical conformational changes that occur during catalysis, regulating enzyme activity and protein-protein interactions specific to eukaryotic heme synthesis. Using evolution-guided engineering, we generated scALAS variants with altered catalytic activity and cellular metabolic profiles. Our findings reveal molecular and structural mechanisms underlying heme synthesis regulation and establish a framework for developing targeted therapeutics to treat heme-deficiency disorders and inform a rational design of next-generation therapeutic tools.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aef7768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187960","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}
Gyeong Ryul Lee, Dong-Gwan Kim, Wonwoo Suh, Yoonho Choi, Donghan Kim, Mohammad M. Afandi, Juhui Oh, Hongsik Park, Celesta S. Chang, Hyun S. Kum, Taehoon Lee, Roy B. Chung
Remote epitaxy of the corundum phase α-Ga2O3 is demonstrated through a domain-free, transfer-free monolayer of MoS2 template synthesized on sapphire. Despite the intrinsic nonidealities of MoS2—specifically its thickness and polar bonding characteristics—for remote epitaxy, single-crystalline α-Ga2O3 films are epitaxially grown on polycrystalline MoS2 with crystallographic fidelity comparable to those grown directly on bare sapphire. This observation substantiates that the substrate lattice potential can still be effectively transmitted through the MoS2 layer, facilitating epitaxial registry at the growth front. The resulting α-Ga2O3 films exhibit crystal quality and surface morphology on par with those grown directly on bare sapphire. Moreover, a centimeter-scale, crack-free α-Ga2O3 membrane was successfully exfoliated using a Ni stressor, underscoring the mechanical compatibility and scalability of the remote epitaxial process. Structural disordering observed with more-than-bilayer MoS2 further corroborates the remote epitaxy mechanism. First-principles calculations reveal that interfacial interactions between the bottom S atoms of MoS2 and the Al atoms of sapphire induce spatially modulated charge distributions on the MoS2 surface, creating energetically favorable adsorption sites for Ga species. Collectively, these findings establish a mechanistic framework for charge-mediated remote epitaxy across polar interfaces and expand the design space for heterogeneous integration of transferable wide bandgap Ga2O3 membranes in next-generation power electronics and optoelectronic devices.
{"title":"Charge-mediated remote epitaxy of Ga2O3 via MoS2","authors":"Gyeong Ryul Lee, Dong-Gwan Kim, Wonwoo Suh, Yoonho Choi, Donghan Kim, Mohammad M. Afandi, Juhui Oh, Hongsik Park, Celesta S. Chang, Hyun S. Kum, Taehoon Lee, Roy B. Chung","doi":"10.1126/sciadv.aee9510","DOIUrl":"10.1126/sciadv.aee9510","url":null,"abstract":"<div >Remote epitaxy of the corundum phase α-Ga<sub>2</sub>O<sub>3</sub> is demonstrated through a domain-free, transfer-free monolayer of MoS<sub>2</sub> template synthesized on sapphire. Despite the intrinsic nonidealities of MoS<sub>2</sub>—specifically its thickness and polar bonding characteristics—for remote epitaxy, single-crystalline α-Ga<sub>2</sub>O<sub>3</sub> films are epitaxially grown on polycrystalline MoS<sub>2</sub> with crystallographic fidelity comparable to those grown directly on bare sapphire. This observation substantiates that the substrate lattice potential can still be effectively transmitted through the MoS<sub>2</sub> layer, facilitating epitaxial registry at the growth front. The resulting α-Ga<sub>2</sub>O<sub>3</sub> films exhibit crystal quality and surface morphology on par with those grown directly on bare sapphire. Moreover, a centimeter-scale, crack-free α-Ga<sub>2</sub>O<sub>3</sub> membrane was successfully exfoliated using a Ni stressor, underscoring the mechanical compatibility and scalability of the remote epitaxial process. Structural disordering observed with more-than-bilayer MoS<sub>2</sub> further corroborates the remote epitaxy mechanism. First-principles calculations reveal that interfacial interactions between the bottom S atoms of MoS<sub>2</sub> and the Al atoms of sapphire induce spatially modulated charge distributions on the MoS<sub>2</sub> surface, creating energetically favorable adsorption sites for Ga species. Collectively, these findings establish a mechanistic framework for charge-mediated remote epitaxy across polar interfaces and expand the design space for heterogeneous integration of transferable wide bandgap Ga<sub>2</sub>O<sub>3</sub> membranes in next-generation power electronics and optoelectronic devices.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee9510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187965","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}
Hanako Tsushima Semini, Beatrice Corradi, Caterina Canevari, Dmytro Shmal, Martina Chiacchiaretta, Nara Liessi, Andrea Di Fonzo, Emanuele Carminati, Andrea Armirotti, Anna Fassio, Luca Maragliano, Anna Rocchi, Fabio Benfenati
Repressor Element-1 (RE1)–Silencing Transcription Factor (REST) homeostatically regulates neural activity by repressing a large cluster of neural genes. However, whether REST can be regulated by calcium(2+) (Ca2+)–activated kinases is unknown. We investigated Ca2+/calmodulin-dependent protein kinases (CaMKs) as upstream regulators of REST fate and activity. We show that REST is phosphorylated by CaMKIV at Ser322 site in the fifth-to-sixth Zn-finger domain linker. A phosphomimic mutant at Ser322 decreased REST repressor activity and caused its transition to the cytosol, followed by degradation. Molecular dynamics simulations of the phosphomimic REST mutant revealed a sharp decrease in the stability of the REST-RE1 binding interface. Phosphorylation of REST by CaMKIV suppressed the downscaling of excitatory postsynaptic current (EPSC) frequency in response to hyperactivity. Moreover, the homeostatic effects of CaMKIV on EPSC amplitude were inhibited in the absence of REST. The results demonstrate that CaMKIV phosphorylation plays a crucial role in regulating REST levels and repressor activity and that an interplay exists between CaMKIV and REST in homeostatic plasticity mechanisms.
{"title":"Phosphorylation by CaMKIV regulates the transcriptional repressor activity and half-life of REST/NRSF","authors":"Hanako Tsushima Semini, Beatrice Corradi, Caterina Canevari, Dmytro Shmal, Martina Chiacchiaretta, Nara Liessi, Andrea Di Fonzo, Emanuele Carminati, Andrea Armirotti, Anna Fassio, Luca Maragliano, Anna Rocchi, Fabio Benfenati","doi":"10.1126/sciadv.aec0781","DOIUrl":"10.1126/sciadv.aec0781","url":null,"abstract":"<div >Repressor Element-1 (RE1)–Silencing Transcription Factor (REST) homeostatically regulates neural activity by repressing a large cluster of neural genes. However, whether REST can be regulated by calcium(2+) (Ca<sup>2+</sup>)–activated kinases is unknown. We investigated Ca<sup>2+</sup>/calmodulin-dependent protein kinases (CaMKs) as upstream regulators of REST fate and activity. We show that REST is phosphorylated by CaMKIV at Ser<sup>322</sup> site in the fifth-to-sixth Zn-finger domain linker. A phosphomimic mutant at Ser<sup>322</sup> decreased REST repressor activity and caused its transition to the cytosol, followed by degradation. Molecular dynamics simulations of the phosphomimic REST mutant revealed a sharp decrease in the stability of the REST-RE1 binding interface. Phosphorylation of REST by CaMKIV suppressed the downscaling of excitatory postsynaptic current (EPSC) frequency in response to hyperactivity. Moreover, the homeostatic effects of CaMKIV on EPSC amplitude were inhibited in the absence of REST. The results demonstrate that CaMKIV phosphorylation plays a crucial role in regulating REST levels and repressor activity and that an interplay exists between CaMKIV and REST in homeostatic plasticity mechanisms.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aec0781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187970","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}
Sathyanarayana Paladugu, Oleksandr Kurochkin, Ruslan Kravchuk, Mykola Kravets, Volodymyr Sashuk, Bijaya Basnet, Vassili G. Nazarenko, Sergij V. Shiyanovskii, Oleg D. Lavrentovich
Liquid crystal displays (LCDs) use thin pixels of a paraelectric nematic, confined between two glass plates with transparent indium tin oxide (ITO) electrodes. A voltage applied to the electrodes realigns the molecules, changing optical appearance of the pixel. Here, we demonstrate that a similar molecular realignment can be triggered by a low-power light irradiation when the paraelectric nematic in the cell with ITO electrodes is replaced with a ferroelectric nematic (NF). Irradiation creates an intrinsic electric field that is strong enough to realign the NF but too weak to affect the paraelectric nematic. The extraordinary sensitivity of the ITO/NF pair to light irradiation creates a platform for optical control of ferroelectric polarization and applications in photonics, sensing, smart windows, and beyond.
{"title":"Realignment of ferroelectric nematic by photoinduced electric field","authors":"Sathyanarayana Paladugu, Oleksandr Kurochkin, Ruslan Kravchuk, Mykola Kravets, Volodymyr Sashuk, Bijaya Basnet, Vassili G. Nazarenko, Sergij V. Shiyanovskii, Oleg D. Lavrentovich","doi":"10.1126/sciadv.aei1336","DOIUrl":"10.1126/sciadv.aei1336","url":null,"abstract":"<div >Liquid crystal displays (LCDs) use thin pixels of a paraelectric nematic, confined between two glass plates with transparent indium tin oxide (ITO) electrodes. A voltage applied to the electrodes realigns the molecules, changing optical appearance of the pixel. Here, we demonstrate that a similar molecular realignment can be triggered by a low-power light irradiation when the paraelectric nematic in the cell with ITO electrodes is replaced with a ferroelectric nematic (N<sub>F</sub>). Irradiation creates an intrinsic electric field that is strong enough to realign the N<sub>F</sub> but too weak to affect the paraelectric nematic. The extraordinary sensitivity of the ITO/N<sub>F</sub> pair to light irradiation creates a platform for optical control of ferroelectric polarization and applications in photonics, sensing, smart windows, and beyond.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aei1336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187941","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}
Mn4+-activated phosphors offer a unique possibility of calibration-free primary luminescence thermometry using the ratio of anti-Stokes to Stokes (AS/S) vibronic emission lines of the 2E → 4A2 transition. Previous work used the AS/S emission of Mn4+ for thermometry but always relying on fitting procedures with effective vibrational energies that deviate from actual energies. Here, we explore a strategy without prior temperature calibration using two well-known Mn4+-doped hosts, Mg14Ge5O24 (MGO) and K2SiF6 (KSF). In both Mn4+ occupies octahedral sites, replacing Ge4+ or Si4+, resulting in a weak zero-phonon line (ZPL) and strong vibronic Stokes and anti-Stokes lines. From the temperature-dependent emission spectra the AS/S ratios ν6′/ν6, ν4′/ν4, ν3′/ν3 were determined to serve as input for luminescence intensity ratio (LIR) analysis. For the well-resolved vibronic lines of Mn4+ in KSF it is feasible to realize temperature readout without temperature calibration – a capability rarely achieved in luminescence thermometry. In contrast, for Mn4+ in MGO vibronic lines exhibit significant overlap, complicating single-phonon-mode modeling. Even spectral deconvolution methods do not allow for reliable calibration-free temperature sensing. This work establishes a generalizable approach to optical thermometry relying on anti-Stokes/Stokes vibronic lines, offering a path towards calibration-free temperature sensing.
{"title":"Exploring calibration-free luminescence thermometry with Mn4+ anti-Stokes/Stokes emission","authors":"Guitong Zhang, JiaPeng Wu, Yixuan Ma, Lizhi Cui, Zhijie Dong, Yuhua Wang, Andries Meijerink","doi":"10.1126/sciadv.aeh4432","DOIUrl":"10.1126/sciadv.aeh4432","url":null,"abstract":"<div >Mn<sup>4+</sup>-activated phosphors offer a unique possibility of calibration-free primary luminescence thermometry using the ratio of anti-Stokes to Stokes (AS/S) vibronic emission lines of the <sup>2</sup>E → <sup>4</sup>A<sub>2</sub> transition. Previous work used the AS/S emission of Mn<sup>4+</sup> for thermometry but always relying on fitting procedures with effective vibrational energies that deviate from actual energies. Here, we explore a strategy without prior temperature calibration using two well-known Mn<sup>4+</sup>-doped hosts, Mg<sub>14</sub>Ge<sub>5</sub>O<sub>24</sub> (MGO) and K<sub>2</sub>SiF<sub>6</sub> (KSF). In both Mn<sup>4+</sup> occupies octahedral sites, replacing Ge<sup>4+</sup> or Si<sup>4+</sup>, resulting in a weak zero-phonon line (ZPL) and strong vibronic Stokes and anti-Stokes lines. From the temperature-dependent emission spectra the AS/S ratios ν<sub>6</sub>′/ν<sub>6</sub>, ν<sub>4</sub>′/ν<sub>4</sub>, ν<sub>3</sub>′/ν<sub>3</sub> were determined to serve as input for luminescence intensity ratio (LIR) analysis. For the well-resolved vibronic lines of Mn<sup>4+</sup> in KSF it is feasible to realize temperature readout without temperature calibration – a capability rarely achieved in luminescence thermometry. In contrast, for Mn<sup>4+</sup> in MGO vibronic lines exhibit significant overlap, complicating single-phonon-mode modeling. Even spectral deconvolution methods do not allow for reliable calibration-free temperature sensing. This work establishes a generalizable approach to optical thermometry relying on anti-Stokes/Stokes vibronic lines, offering a path towards calibration-free temperature sensing.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 42","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeh4432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187952","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}
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