Eun Chae Moon, Tushar Modi, Dong-yeon D. Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan, Gürol M. Süel
Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of Bacillus subtilis and identified a Mg2+-dependent physiological cost. Coculture competition experiments show that Mg2+ limitation hinders the growth of the L22* variant more than the wild type (WT), even under antibiotic pressure. This growth disadvantage of L22* cells is not due to lower ribosome abundance but rather due to reduced intracellular Mg2+ levels. Coarse-grained elastic-network modeling of ribosome conformational dynamics suggests that L22* ribosomes associate more tightly with Mg2+ when compared to WT. We combined the structural modeling and experimental measurements in a steady-state model to predict cellular adenosine 5′-triphosphate (ATP) levels, which also depend on Mg2+. Experiments confirmed a predicted ATP drop in L22* cells under Mg2+ limitation, while WT cells were less affected. Intracellular competition for a finite Mg2+ pool can thus suppress the establishment of an antibiotic-resistant ribosome variant.
{"title":"Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria","authors":"Eun Chae Moon, Tushar Modi, Dong-yeon D. Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan, Gürol M. Süel","doi":"10.1126/sciadv.adq5249","DOIUrl":"10.1126/sciadv.adq5249","url":null,"abstract":"<div >Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of <i>Bacillus subtilis</i> and identified a Mg<sup>2+</sup>-dependent physiological cost. Coculture competition experiments show that Mg<sup>2+</sup> limitation hinders the growth of the L22* variant more than the wild type (WT), even under antibiotic pressure. This growth disadvantage of L22* cells is not due to lower ribosome abundance but rather due to reduced intracellular Mg<sup>2+</sup> levels. Coarse-grained elastic-network modeling of ribosome conformational dynamics suggests that L22* ribosomes associate more tightly with Mg<sup>2+</sup> when compared to WT. We combined the structural modeling and experimental measurements in a steady-state model to predict cellular adenosine 5′-triphosphate (ATP) levels, which also depend on Mg<sup>2+</sup>. Experiments confirmed a predicted ATP drop in L22* cells under Mg<sup>2+</sup> limitation, while WT cells were less affected. Intracellular competition for a finite Mg<sup>2+</sup> pool can thus suppress the establishment of an antibiotic-resistant ribosome variant.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq5249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637769","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}
Nathaniel Oberholtzer, Paramita Chakraborty, Mohamed Faisal Kassir, James Dressman, Satyajit Das, Stephanie Mills, Susana Comte-Walters, Monika Gooz, Seungho Choi, Rasesh Y. Parikh, Zacharia Hedley, Silvia Vaena, Reid DeMass, Gina Scurti, Martin Romeo, Vamsi K. Gangaraju, Stefano Berto, Elizabeth Hill, Lauren E. Ball, Anand S. Mehta, Eduardo N. Maldonado, Michael I. Nishimura, Besim Ogretmen, Shikhar Mehrotra
The role of tumor microenvironment (TME)–associated inadequate protein modification and trafficking due to insufficiency in Golgi function, leading to Golgi stress, in the regulation of T cell function is largely unknown. Here, we show that disruption of Golgi architecture under TME stress, identified by the decreased expression of GM130, was reverted upon treatment with hydrogen sulfide (H2S) donor GYY4137 or overexpressing cystathionine β-synthase (CBS), an enzyme involved in the biosynthesis of endogenous H2S, which also promoted stemness, antioxidant capacity, and increased protein translation, mediated in part by endoplasmic reticulum–Golgi shuttling of Peroxiredoxin-4. In in vivo models of melanoma and lymphoma, antitumor T cells conditioned ex vivo with exogenous H2S or overexpressing CBS demonstrated superior tumor control upon adoptive transfer. Further, T cells with high Golgi content exhibited unique metabolic and glycation signatures with enhanced antitumor capacity. These data suggest that strategies to mitigate Golgi network stress or using Golgihi tumor-reactive T cells can improve tumor control upon adoptive transfer.
肿瘤微环境（TME）与高尔基体功能不足导致的蛋白质修饰和转运不足有关，从而导致高尔基体应激，而高尔基体应激在调控 T 细胞功能中的作用在很大程度上是未知的。在这里，我们发现，在硫化氢（H 2 S）供体 GYY4137 处理或过表达胱硫醚 β 合成酶（CBS）后，TME 应激下高尔基体结构的破坏（由 GM130 的表达减少确定）被逆转、这也促进了干性、抗氧化能力和蛋白质翻译的增加，部分是由内质网-高尔基体穿梭的过氧化还原酶-4介导的。在黑色素瘤和淋巴瘤的活体模型中，用外源 H 2 S 或过表达 CBS 的抗肿瘤 T 细胞在进行收养性转移时显示出卓越的肿瘤控制能力。此外，高尔基体含量高的 T 细胞表现出独特的代谢和糖化特征，具有更强的抗肿瘤能力。这些数据表明，减轻高尔基体网络压力或使用高尔基体高肿瘤反应性 T 细胞的策略可以提高肿瘤控制能力。
{"title":"H2S-Prdx4 axis mitigates Golgi stress to bolster tumor-reactive T cell immunotherapeutic response","authors":"Nathaniel Oberholtzer, Paramita Chakraborty, Mohamed Faisal Kassir, James Dressman, Satyajit Das, Stephanie Mills, Susana Comte-Walters, Monika Gooz, Seungho Choi, Rasesh Y. Parikh, Zacharia Hedley, Silvia Vaena, Reid DeMass, Gina Scurti, Martin Romeo, Vamsi K. Gangaraju, Stefano Berto, Elizabeth Hill, Lauren E. Ball, Anand S. Mehta, Eduardo N. Maldonado, Michael I. Nishimura, Besim Ogretmen, Shikhar Mehrotra","doi":"10.1126/sciadv.adp1152","DOIUrl":"10.1126/sciadv.adp1152","url":null,"abstract":"<div >The role of tumor microenvironment (TME)–associated inadequate protein modification and trafficking due to insufficiency in Golgi function, leading to Golgi stress, in the regulation of T cell function is largely unknown. Here, we show that disruption of Golgi architecture under TME stress, identified by the decreased expression of GM130, was reverted upon treatment with hydrogen sulfide (H<sub>2</sub>S) donor GYY4137 or overexpressing cystathionine β-synthase (CBS), an enzyme involved in the biosynthesis of endogenous H<sub>2</sub>S, which also promoted stemness, antioxidant capacity, and increased protein translation, mediated in part by endoplasmic reticulum–Golgi shuttling of Peroxiredoxin-4. In in vivo models of melanoma and lymphoma, antitumor T cells conditioned ex vivo with exogenous H<sub>2</sub>S or overexpressing CBS demonstrated superior tumor control upon adoptive transfer. Further, T cells with high Golgi content exhibited unique metabolic and glycation signatures with enhanced antitumor capacity. These data suggest that strategies to mitigate Golgi network stress or using Golgi<sup>hi</sup> tumor-reactive T cells can improve tumor control upon adoptive transfer.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp1152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637849","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}
Sujeong Kim, Hyeongwoo Lee, Seonhye Eom, Gangseon Ji, Soo Ho Choi, Huitae Joo, Jinhyuk Bae, Ki Kang Kim, Hyeong-Ryeol Park, Kyoung-Duck Park
Controlling electron density in two-dimensional semiconductors is crucial for both comprehensive understanding of fundamental material properties and their technological applications. However, conventional electrostatic doping methods exhibit limitations, particularly in addressing electric field–induced drift and subsequent diffusion of electrons, which restrict nanoscale doping. Here, we present a tip-induced nanospectroscopic electric pulse modulator to dynamically control nanoscale electron density, thereby facilitating precise measurement of nano-optoelectronic behaviors within a MoS2 monolayer. The tip-induced electric pulse enables nanoscale modulation of electron distribution as a function of electric pulse width. We simultaneously investigate spatially altering photoluminescence quantum yield at the nanoscale region. We model the extent of electron depletion region, confirming a minimum doping region with a radius of ∼265 nanometers for a 30-nanosecond pulse width. Our approach paves the way for engineering local electron density and in situ nano-optical characterization in two-dimensional materials, enabling an in-depth understanding of doping-dependent nano-optoelectronic phenomena.
控制二维半导体中的电子密度对于全面了解材料的基本特性及其技术应用至关重要。然而，传统的静电掺杂方法存在局限性，尤其是在解决电场诱导的电子漂移和随后的电子扩散方面，这限制了纳米尺度的掺杂。在这里，我们提出了一种尖端诱导纳米光谱电脉冲调制器，用于动态控制纳米级电子密度，从而促进 MoS 2 单层内纳米光电行为的精确测量。尖端诱导的电脉冲能以电脉冲宽度的函数对电子分布进行纳米级调制。同时，我们还研究了纳米尺度区域光致发光量子产率的空间变化。我们对电子耗尽区的范围进行了建模，确认了在 30 纳秒脉冲宽度下半径为 ∼ 265 纳米的最小掺杂区。我们的方法为二维材料中的局部电子密度工程和原位纳米光学表征铺平了道路，使人们能够深入了解依赖于掺杂的纳米光电现象。
{"title":"Dynamical control of nanoscale electron density in atomically thin n-type semiconductors via nano-electric pulse generator","authors":"Sujeong Kim, Hyeongwoo Lee, Seonhye Eom, Gangseon Ji, Soo Ho Choi, Huitae Joo, Jinhyuk Bae, Ki Kang Kim, Hyeong-Ryeol Park, Kyoung-Duck Park","doi":"10.1126/sciadv.adr0492","DOIUrl":"10.1126/sciadv.adr0492","url":null,"abstract":"<div >Controlling electron density in two-dimensional semiconductors is crucial for both comprehensive understanding of fundamental material properties and their technological applications. However, conventional electrostatic doping methods exhibit limitations, particularly in addressing electric field–induced drift and subsequent diffusion of electrons, which restrict nanoscale doping. Here, we present a tip-induced nanospectroscopic electric pulse modulator to dynamically control nanoscale electron density, thereby facilitating precise measurement of nano-optoelectronic behaviors within a MoS<sub>2</sub> monolayer. The tip-induced electric pulse enables nanoscale modulation of electron distribution as a function of electric pulse width. We simultaneously investigate spatially altering photoluminescence quantum yield at the nanoscale region. We model the extent of electron depletion region, confirming a minimum doping region with a radius of ∼265 nanometers for a 30-nanosecond pulse width. Our approach paves the way for engineering local electron density and in situ nano-optical characterization in two-dimensional materials, enabling an in-depth understanding of doping-dependent nano-optoelectronic phenomena.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr0492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637704","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}
Wenjing Lv, Haoye Qin, Zengping Su, Chengzhi Zhang, Jiongpeng Huang, Yuzhi Shi, Bo Li, Patrice Genevet, Qinghua Song
C points, circular polarization in momentum space, play crucial roles in chiral wave manipulations. However, conventional approaches of achieving intrinsic C points using photonic crystals with broken symmetries suffer from a low Q factor and high sensitivity to structural geometry, rendering them fragile and susceptible to perturbations and disorders. We report magneto-optical (MO) bound states in the continuum (BICs) with a symmetry-preserved planar photonic crystal. We achieve intrinsic C points at Γ point that are robust against variation in both structural geometry and external magnetic field. MO coupling between two modes induces Zeeman splitting, leading to MO BICs and quasi-BICs with circular eigenstates for high-Q chiral responses. Furthermore, switchable C point handedness and circular dichroism are enabled by reversing the magnetic field. These findings unveil BICs and quasi-BICs with circular eigenstates and on-demand control of C points, paving the way for advanced chiral wave manipulation with enhanced light-matter interaction.
C 点是动量空间中的圆偏振，在手性波操纵中发挥着至关重要的作用。然而，利用对称性被破坏的光子晶体实现本征 C 点的传统方法存在 Q 值系数低和对结构几何高度敏感的问题，这使得它们非常脆弱，容易受到扰动和紊乱的影响。我们利用对称性保留的平面光子晶体报告了连续体中的磁光（MO）束缚态（BICs）。我们在 Γ 点实现了本征 C 点，它对结构几何和外部磁场的变化都很稳定。两种模式之间的 MO 耦合会诱发泽曼分裂，从而产生 MO BIC 和准 BIC，并具有高 Q 手性响应的圆形特征态。此外，通过反转磁场还能实现可切换的 C 点手性和圆二色性。这些发现揭示了具有圆特征状态和按需控制 C 点的 BIC 和准 BIC，为增强光-物质相互作用的先进手性波操纵铺平了道路。
{"title":"Robust generation of intrinsic C points with magneto-optical bound states in the continuum","authors":"Wenjing Lv, Haoye Qin, Zengping Su, Chengzhi Zhang, Jiongpeng Huang, Yuzhi Shi, Bo Li, Patrice Genevet, Qinghua Song","doi":"10.1126/sciadv.ads0157","DOIUrl":"10.1126/sciadv.ads0157","url":null,"abstract":"<div >C points, circular polarization in momentum space, play crucial roles in chiral wave manipulations. However, conventional approaches of achieving intrinsic C points using photonic crystals with broken symmetries suffer from a low <i>Q</i> factor and high sensitivity to structural geometry, rendering them fragile and susceptible to perturbations and disorders. We report magneto-optical (MO) bound states in the continuum (BICs) with a symmetry-preserved planar photonic crystal. We achieve intrinsic C points at Γ point that are robust against variation in both structural geometry and external magnetic field. MO coupling between two modes induces Zeeman splitting, leading to MO BICs and quasi-BICs with circular eigenstates for high-<i>Q</i> chiral responses. Furthermore, switchable C point handedness and circular dichroism are enabled by reversing the magnetic field. These findings unveil BICs and quasi-BICs with circular eigenstates and on-demand control of C points, paving the way for advanced chiral wave manipulation with enhanced light-matter interaction.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads0157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637768","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}
Carla Huerta-López, Alejandro Clemente-Manteca, Diana Velázquez-Carreras, Francisco M. Espinosa, Juan G. Sanchez, Álvaro Martínez-del-Pozo, María García-García, Sara Martín-Colomo, Andrea Rodríguez-Blanco, Ricardo Esteban-González, Francisco M. Martín-Zamora, Luis I. Gutierrez-Rus, Ricardo Garcia, Pere Roca-Cusachs, Alberto Elosegui-Artola, Miguel A. del Pozo, Elías Herrero-Galán, Pablo Sáez, Gustavo R. Plaza, Jorge Alegre-Cebollada
The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch–based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM.
{"title":"Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing","authors":"Carla Huerta-López, Alejandro Clemente-Manteca, Diana Velázquez-Carreras, Francisco M. Espinosa, Juan G. Sanchez, Álvaro Martínez-del-Pozo, María García-García, Sara Martín-Colomo, Andrea Rodríguez-Blanco, Ricardo Esteban-González, Francisco M. Martín-Zamora, Luis I. Gutierrez-Rus, Ricardo Garcia, Pere Roca-Cusachs, Alberto Elosegui-Artola, Miguel A. del Pozo, Elías Herrero-Galán, Pablo Sáez, Gustavo R. Plaza, Jorge Alegre-Cebollada","doi":"10.1126/sciadv.adf9758","DOIUrl":"10.1126/sciadv.adf9758","url":null,"abstract":"<div >The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch–based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adf9758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637706","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}
Qianqian Li, Jian Liu, Liping Guo, Yi Zhang, Yanwei Chen, Huijuan Liu, Hongyu Cheng, Lin Deng, Juhui Qiu, Ke Zhang, Wee Siong Sho Goh, Yingxiao Wang, Qin Peng
N6-methyladenosine (m6A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m6A modification and SG stability remains unclear. Here, we presented a spatiotemporal m6A imaging system (SMIS) that can monitor the m6A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed that m6A-modified reporter mRNAs dynamically enriched into SGs under arsenite stress and gradually partitioned into the cytosol as SG disassembled. SMIS revealed that knockdown of YTHDF2 contributed to SG disassembly, resulting in the fast redistribution of mRNAs from SGs and rapid recovery of stalled translation. The mechanism is that YTHDF2 can regulate SG stability through the interaction with G3BP1 in m6A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay between m6A modification and SG through YTHDF2 regulation.
N 6 -甲基腺苷（m 6 A）修饰的mRNA及其胞质阅读器YTHDFs在应激条件下与应激颗粒（SG）共定位，但m 6 A修饰与SG稳定性之间的相互作用仍不清楚。在这里，我们展示了一种时空 m 6 A 成像系统（SMIS），它能在单个活细胞中以高特异性和高灵敏度监测 m 6 A 修饰和 mRNA 的翻译。SMIS显示，在亚砷酸盐胁迫下，m 6 A修饰的报告基因mRNA动态地富集到SG中，并随着SG的解体逐渐进入细胞质。SMIS发现，YTHDF2的敲除有助于SG的解体，导致mRNA从SG中快速重新分布，并使停滞的翻译迅速恢复。其机制是YTHDF2通过与G3BP1相互作用，以m 6 A修饰RNA依赖的方式调节SG的稳定性。我们的研究结果表明，m 6 A修饰与SG之间的相互作用机制是通过YTHDF2调控的。
{"title":"Decoding the interplay between m6A modification and stress granule stability by live-cell imaging","authors":"Qianqian Li, Jian Liu, Liping Guo, Yi Zhang, Yanwei Chen, Huijuan Liu, Hongyu Cheng, Lin Deng, Juhui Qiu, Ke Zhang, Wee Siong Sho Goh, Yingxiao Wang, Qin Peng","doi":"10.1126/sciadv.adp5689","DOIUrl":"10.1126/sciadv.adp5689","url":null,"abstract":"<div ><i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m<sup>6</sup>A modification and SG stability remains unclear. Here, we presented a spatiotemporal m<sup>6</sup>A imaging system (SMIS) that can monitor the m<sup>6</sup>A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed that m<sup>6</sup>A-modified reporter mRNAs dynamically enriched into SGs under arsenite stress and gradually partitioned into the cytosol as SG disassembled. SMIS revealed that knockdown of YTHDF2 contributed to SG disassembly, resulting in the fast redistribution of mRNAs from SGs and rapid recovery of stalled translation. The mechanism is that YTHDF2 can regulate SG stability through the interaction with G3BP1 in m<sup>6</sup>A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay between m<sup>6</sup>A modification and SG through YTHDF2 regulation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp5689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637713","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}
Samantha L. Yaussy, Kathryn E. Marklein, Sharon N. DeWitte, Douglas E. Crews
Bioarchaeology uses human skeletal remains to reconstruct varied experiences of individuals and populations in the past, including patterns of health across time periods and cultural contexts. In the past three decades, bioarchaeological studies have highlighted the concept of “frailty,” operationalizing it as increased risk of mortality or cumulative phenotypes. Using data from medieval London cemeteries, we integrate these two approaches to frailty in past populations. First, we estimate the risks of mortality and survivorship (hazard and survival analyses) associated with 10 biomarkers and use these results to construct population-specific frailty and resilience indices. Then, we apply the indices to adult individuals to explore frailty and resilience differentials between males and females in medieval London. Findings suggest that the male-female morbidity-mortality paradox observed in modern populations may not have existed in this context, which may be explained by preferential cultural buffering of men in this patriarchal, urban setting.
{"title":"Frailty or resilience? Hazard-based and cumulative phenotype approaches to discerning signals of health inequality in medieval London","authors":"Samantha L. Yaussy, Kathryn E. Marklein, Sharon N. DeWitte, Douglas E. Crews","doi":"10.1126/sciadv.adq5703","DOIUrl":"10.1126/sciadv.adq5703","url":null,"abstract":"<div >Bioarchaeology uses human skeletal remains to reconstruct varied experiences of individuals and populations in the past, including patterns of health across time periods and cultural contexts. In the past three decades, bioarchaeological studies have highlighted the concept of “frailty,” operationalizing it as increased risk of mortality or cumulative phenotypes. Using data from medieval London cemeteries, we integrate these two approaches to frailty in past populations. First, we estimate the risks of mortality and survivorship (hazard and survival analyses) associated with 10 biomarkers and use these results to construct population-specific frailty and resilience indices. Then, we apply the indices to adult individuals to explore frailty and resilience differentials between males and females in medieval London. Findings suggest that the male-female morbidity-mortality paradox observed in modern populations may not have existed in this context, which may be explained by preferential cultural buffering of men in this patriarchal, urban setting.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq5703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602004","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}
The coastal circulation around Southern Greenland transports fresh, buoyant water masses from the Arctic and Greenland Ice Sheet near regions of convection, sinking, and deep-water formation in the Irminger and Labrador Seas. Here, we track the pathways and fate of these fresh water masses by initializing synthetic particles in the East Greenland Coastal Current on the Southeast Greenland shelf and running them through altimetry-derived surface currents from 1993 to 2021. We report that the majority of waters (83%) remain on the shelf around the southern tip of Greenland. Variability in the shelf-basin exchange of the remaining particles closely follows the number of tip jet wind events on seasonal and interannual timescales. The probability of a particle exiting the shelf increases almost fivefold during a tip jet event. These results indicate that the number of tip jets is a close proxy of the shelf-basin exchange around Southern Greenland.
{"title":"Extreme wind events responsible for an outsized role in shelf-basin exchange around the southern tip of Greenland","authors":"Arthur Coquereau, Nicholas P. Foukal, Kjetil Våge","doi":"10.1126/sciadv.adp9266","DOIUrl":"10.1126/sciadv.adp9266","url":null,"abstract":"<div >The coastal circulation around Southern Greenland transports fresh, buoyant water masses from the Arctic and Greenland Ice Sheet near regions of convection, sinking, and deep-water formation in the Irminger and Labrador Seas. Here, we track the pathways and fate of these fresh water masses by initializing synthetic particles in the East Greenland Coastal Current on the Southeast Greenland shelf and running them through altimetry-derived surface currents from 1993 to 2021. We report that the majority of waters (83%) remain on the shelf around the southern tip of Greenland. Variability in the shelf-basin exchange of the remaining particles closely follows the number of tip jet wind events on seasonal and interannual timescales. The probability of a particle exiting the shelf increases almost fivefold during a tip jet event. These results indicate that the number of tip jets is a close proxy of the shelf-basin exchange around Southern Greenland.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp9266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602020","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}
Tong Ying, Jing Li, Qiang Fu, Guanyu Liu, Lu Zhang, Yan Xia, Yongyun Hu
The relative amount of scattering and absorbing aerosols is essential in determining the aerosol radiative and climate effects. Using reanalysis datasets and climate simulations, here, we show that changes in the relative amount of scattering and absorbing aerosols in the Northern Hemisphere (NH) high latitudes, manifested as long-term decreasing trends in aerosol single-scattering albedo (SSA), have played an important role in driving the widening and weakening trends of the NH Hadley circulation (HC) since the early 1980s. Decreasing SSA in the NH middle and high latitudes can notably warm the troposphere there, thus reducing the equator-to-pole temperature gradient, increasing static stability in mid-latitude regions, and leading to the widening and weakening trends of NH HC. Further analysis of the Coupled Model Intercomparison Project Phase 6 (CMIP6) aerosol forcing–only simulations also supports the importance of SSA trends in perturbing NH HC through the above mechanism.
{"title":"Fractional change of scattering and absorbing aerosols contributes to Northern Hemisphere Hadley circulation expansion","authors":"Tong Ying, Jing Li, Qiang Fu, Guanyu Liu, Lu Zhang, Yan Xia, Yongyun Hu","doi":"10.1126/sciadv.adq9716","DOIUrl":"10.1126/sciadv.adq9716","url":null,"abstract":"<div >The relative amount of scattering and absorbing aerosols is essential in determining the aerosol radiative and climate effects. Using reanalysis datasets and climate simulations, here, we show that changes in the relative amount of scattering and absorbing aerosols in the Northern Hemisphere (NH) high latitudes, manifested as long-term decreasing trends in aerosol single-scattering albedo (SSA), have played an important role in driving the widening and weakening trends of the NH Hadley circulation (HC) since the early 1980s. Decreasing SSA in the NH middle and high latitudes can notably warm the troposphere there, thus reducing the equator-to-pole temperature gradient, increasing static stability in mid-latitude regions, and leading to the widening and weakening trends of NH HC. Further analysis of the Coupled Model Intercomparison Project Phase 6 (CMIP6) aerosol forcing–only simulations also supports the importance of SSA trends in perturbing NH HC through the above mechanism.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq9716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602012","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}
Marius Sandru, Marie Prache, Thomas Macron, Lidia Căta, Mehmet Göktuğ Ahunbay, May-Britt Hägg, Guillaume Maurin, Mihail Barboiu
The capture of CO2 is of high interest in our society representing an essential tool to mitigate man-made climate warming. Membrane technology applied for CO2 capture offers several advantages in terms of energy savings, simple operation, and easy scale-up. Glassy membranes are associated with low gas permeability that negatively affect on their industrial implementation. Oppositely, rubbery membranes offer high permeability, but their selectivity is low. Here we report rubbery organic frameworks (ROFs) combining the high permeability of soft matrices with the high sieving selectivity of molecular frameworks. The best performing membranes provide a CO2/N2 selectivity up to 104 with a CO2 permeability up to 1000 Barrer, representing relevant performances for industrial implementation. Water vapors have a positive effect on CO2 permeability, and the CO2/N2 selectivity is higher than in dry conditions, as most of CO2 gas emissions are present in fully humidified gas streams. The synergetic high permeability/selectivity performances are superior to that observed with current state-of-the-art polymeric membranes.
二氧化碳捕集是我们社会高度关注的问题，是减缓人为气候变暖的重要工具。应用于二氧化碳捕集的膜技术在节能、操作简单和易于放大等方面具有多项优势。玻璃膜的气体渗透性较低，这对其工业应用产生了负面影响。相反，橡胶膜具有高渗透性，但其选择性较低。我们在此报告的橡胶有机框架（ROFs）结合了软基质的高渗透性和分子框架的高筛分选择性。性能最好的膜可提供高达 104 的 CO 2 /N 2 选择性和高达 1000 巴勒的 CO 2 渗透性，代表了工业应用的相关性能。水蒸气对 CO 2 的渗透性有积极影响，CO 2 /N 2 的选择性高于干燥条件下的选择性，因为大部分 CO 2 气体排放都存在于完全加湿的气流中。高渗透性/选择性的协同性能优于目前最先进的聚合膜。
{"title":"Rubbery organic frameworks (ROFs) toward ultrapermeable CO2-selective membranes","authors":"Marius Sandru, Marie Prache, Thomas Macron, Lidia Căta, Mehmet Göktuğ Ahunbay, May-Britt Hägg, Guillaume Maurin, Mihail Barboiu","doi":"10.1126/sciadv.adq5024","DOIUrl":"10.1126/sciadv.adq5024","url":null,"abstract":"<div >The capture of CO<sub>2</sub> is of high interest in our society representing an essential tool to mitigate man-made climate warming. Membrane technology applied for CO<sub>2</sub> capture offers several advantages in terms of energy savings, simple operation, and easy scale-up. Glassy membranes are associated with low gas permeability that negatively affect on their industrial implementation. Oppositely, rubbery membranes offer high permeability, but their selectivity is low. Here we report rubbery organic frameworks (ROFs) combining the high permeability of soft matrices with the high sieving selectivity of molecular frameworks. The best performing membranes provide a CO<sub>2</sub>/N<sub>2</sub> selectivity up to 104 with a CO<sub>2</sub> permeability up to 1000 Barrer, representing relevant performances for industrial implementation. Water vapors have a positive effect on CO<sub>2</sub> permeability, and the CO<sub>2</sub>/N<sub>2</sub> selectivity is higher than in dry conditions, as most of CO<sub>2</sub> gas emissions are present in fully humidified gas streams. The synergetic high permeability/selectivity performances are superior to that observed with current state-of-the-art polymeric membranes.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 46","pages":""},"PeriodicalIF":11.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq5024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602006","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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