Mo Chen, John Clai Owens, Harald Putterman, Max Schäfer, Oskar Painter
Noise within solid-state systems at low temperatures can typically be traced back to material defects. In amorphous materials, these defects are broadly described by the tunneling two-level systems (TLSs) model. TLS have recently taken on further relevance in quantum computing because they dominate the coherence limit of superconducting quantum circuits. Efforts to mitigate TLS impacts have thus far focused on circuit design, material selection, and surface treatments. Our work takes an approach that directly modifies TLS properties. This is achieved by creating an acoustic bandgap that suppresses all microwave-frequency phonons around the operating frequency of a transmon qubit. For embedded TLS strongly coupled to the transmon qubit, we measure a pronounced increase in relaxation time by two orders of magnitude, with the longest T1 time exceeding 5 milliseconds. Our work opens avenues for studying the physics of highly coherent TLS and methods for mitigating noise within solid-state quantum devices.
{"title":"Phonon engineering of atomic-scale defects in superconducting quantum circuits","authors":"Mo Chen, John Clai Owens, Harald Putterman, Max Schäfer, Oskar Painter","doi":"10.1126/sciadv.ado6240","DOIUrl":"10.1126/sciadv.ado6240","url":null,"abstract":"<div >Noise within solid-state systems at low temperatures can typically be traced back to material defects. In amorphous materials, these defects are broadly described by the tunneling two-level systems (TLSs) model. TLS have recently taken on further relevance in quantum computing because they dominate the coherence limit of superconducting quantum circuits. Efforts to mitigate TLS impacts have thus far focused on circuit design, material selection, and surface treatments. Our work takes an approach that directly modifies TLS properties. This is achieved by creating an acoustic bandgap that suppresses all microwave-frequency phonons around the operating frequency of a transmon qubit. For embedded TLS strongly coupled to the transmon qubit, we measure a pronounced increase in relaxation time by two orders of magnitude, with the longest <i>T</i><sub>1</sub> time exceeding 5 milliseconds. Our work opens avenues for studying the physics of highly coherent TLS and methods for mitigating noise within solid-state quantum devices.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado6240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231173","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}
Samuel E. J. Preston, Michael S. Dahabieh, Raúl Ernesto Flores González, Christophe Gonçalves, Vincent R. Richard, Matthew Leibovitch, Eleanor Dakin, Theodore Papadopoulos, Carolina Lopez Naranjo, Paige A. McCallum, Fan Huang, Natascha Gagnon, Stephanie Perrino, René P. Zahedi, Christoph H. Borchers, Russell G. Jones, Pnina Brodt, Wilson H. Miller Jr., Sonia V. del Rincón
Dysregulation of the mitogen-activated protein kinase interacting kinases 1/2 (MNK1/2)–eukaryotic initiation factor 4E (eIF4E) signaling axis promotes breast cancer progression. MNK1 is known to influence cancer stem cells (CSCs); self-renewing populations that support metastasis, recurrence, and chemotherapeutic resistance, making them a clinically relevant target. The precise function of MNK1 in regulating CSCs, however, remains unexplored. Here, we generated MNK1 knockout cancer cell lines, resulting in diminished CSC properties in vitro and slowed tumor growth in vivo. Using a multiomics approach, we functionally demonstrated that loss of MNK1 restricts tumor cell metabolic adaptation by reducing glycolysis and increasing dependence on oxidative phosphorylation. Furthermore, MNK1-null breast and pancreatic tumor cells demonstrated suppressed metastasis to the liver, but not the lung. Analysis of The Cancer Genome Atlas (TCGA) data from breast cancer patients validated the positive correlation between MNK1 and glycolytic enzyme protein expression. This study defines metabolic perturbations as a previously unknown consequence of targeting MNK1/2, which may be therapeutically exploited.
{"title":"Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis","authors":"Samuel E. J. Preston, Michael S. Dahabieh, Raúl Ernesto Flores González, Christophe Gonçalves, Vincent R. Richard, Matthew Leibovitch, Eleanor Dakin, Theodore Papadopoulos, Carolina Lopez Naranjo, Paige A. McCallum, Fan Huang, Natascha Gagnon, Stephanie Perrino, René P. Zahedi, Christoph H. Borchers, Russell G. Jones, Pnina Brodt, Wilson H. Miller Jr., Sonia V. del Rincón","doi":"10.1126/sciadv.adi7673","DOIUrl":"10.1126/sciadv.adi7673","url":null,"abstract":"<div >Dysregulation of the mitogen-activated protein kinase interacting kinases 1/2 (MNK1/2)–eukaryotic initiation factor 4E (eIF4E) signaling axis promotes breast cancer progression. MNK1 is known to influence cancer stem cells (CSCs); self-renewing populations that support metastasis, recurrence, and chemotherapeutic resistance, making them a clinically relevant target. The precise function of MNK1 in regulating CSCs, however, remains unexplored. Here, we generated MNK1 knockout cancer cell lines, resulting in diminished CSC properties in vitro and slowed tumor growth in vivo. Using a multiomics approach, we functionally demonstrated that loss of MNK1 restricts tumor cell metabolic adaptation by reducing glycolysis and increasing dependence on oxidative phosphorylation. Furthermore, MNK1-null breast and pancreatic tumor cells demonstrated suppressed metastasis to the liver, but not the lung. Analysis of The Cancer Genome Atlas (TCGA) data from breast cancer patients validated the positive correlation between MNK1 and glycolytic enzyme protein expression. This study defines metabolic perturbations as a previously unknown consequence of targeting MNK1/2, which may be therapeutically exploited.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adi7673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231181","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}
Radiogenic heat production is fundamental to the energy budget of planets. Roughly half of the heat that Earth loses through its surface today comes from the three long-lived, heat-producing elements (potassium, thorium, and uranium). These three elements have long been believed to be highly lithophile and thus concentrate in the mantle of rocky planets. However, our study shows that they all become siderophile under the pressure and temperature conditions relevant to the core formation of large rocky planets dubbed super-Earths. Mantle convection in super-Earths is then primarily driven by heating from the core rather than by a mix of internal heating and cooling from above as in Earth. Partitioning these sources of radiogenic heat into the core remarkably increases the core-mantle boundary (CMB) temperature and the total heat flow across the CMB in super-Earths. Consequently, super-Earths are likely to host long-lived volcanism and strong magnetic dynamos.
{"title":"Radiogenic heating sustains long-lived volcanism and magnetic dynamos in super-Earths","authors":"Haiyang Luo, Joseph G. O’Rourke, Jie Deng","doi":"10.1126/sciadv.ado7603","DOIUrl":"10.1126/sciadv.ado7603","url":null,"abstract":"<div >Radiogenic heat production is fundamental to the energy budget of planets. Roughly half of the heat that Earth loses through its surface today comes from the three long-lived, heat-producing elements (potassium, thorium, and uranium). These three elements have long been believed to be highly lithophile and thus concentrate in the mantle of rocky planets. However, our study shows that they all become siderophile under the pressure and temperature conditions relevant to the core formation of large rocky planets dubbed super-Earths. Mantle convection in super-Earths is then primarily driven by heating from the core rather than by a mix of internal heating and cooling from above as in Earth. Partitioning these sources of radiogenic heat into the core remarkably increases the core-mantle boundary (CMB) temperature and the total heat flow across the CMB in super-Earths. Consequently, super-Earths are likely to host long-lived volcanism and strong magnetic dynamos.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado7603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231178","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}
Katsunori Tamagawa, Mehmet Dayi, Simo Sun, Rikako Hata, Taisei Kikuchi, Nami Haruta, Asako Sugimoto, Takashi Makino
The transition of the sexual mode occurs widely in animal evolution. In Caenorhabditis nematodes, androdioecy, a sexual polymorphism composed of males and hermaphrodites having the ability to self-fertilize, has evolved independently multiple times. While the modification of noncoding regulatory elements likely contributed to the evolution of hermaphroditism, little is known about these changes. Here, we conducted a genome-wide analysis of conserved noncoding elements (CNEs) focusing on the evolution of hermaphroditism in Caenorhabditis nematodes. We found that, in androdioecious nematodes, mutations rapidly accumulated in CNEs’ neighboring genes associated with sexual traits. Expression analysis indicate that the identified CNEs are involved in spermatogenesis in hermaphrodites and associated with the transition of gene expression from dioecious to androdioecious nematodes. Last, genome editing of a CNE neighboring laf-1 resulted in a change in its expression in the gonadal region undergoing spermatogenesis. Our bioinformatic and experimental analyses highlight the importance of CNEs in gene regulation associated with the development of hermaphrodites.
{"title":"Evolutionary changes of noncoding elements associated with transition of sexual mode in Caenorhabditis nematodes","authors":"Katsunori Tamagawa, Mehmet Dayi, Simo Sun, Rikako Hata, Taisei Kikuchi, Nami Haruta, Asako Sugimoto, Takashi Makino","doi":"10.1126/sciadv.adn9913","DOIUrl":"10.1126/sciadv.adn9913","url":null,"abstract":"<div >The transition of the sexual mode occurs widely in animal evolution. In <i>Caenorhabditis</i> nematodes, androdioecy, a sexual polymorphism composed of males and hermaphrodites having the ability to self-fertilize, has evolved independently multiple times. While the modification of noncoding regulatory elements likely contributed to the evolution of hermaphroditism, little is known about these changes. Here, we conducted a genome-wide analysis of conserved noncoding elements (CNEs) focusing on the evolution of hermaphroditism in <i>Caenorhabditis</i> nematodes. We found that, in androdioecious nematodes, mutations rapidly accumulated in CNEs’ neighboring genes associated with sexual traits. Expression analysis indicate that the identified CNEs are involved in spermatogenesis in hermaphrodites and associated with the transition of gene expression from dioecious to androdioecious nematodes. Last, genome editing of a CNE neighboring <i>laf-1</i> resulted in a change in its expression in the gonadal region undergoing spermatogenesis. Our bioinformatic and experimental analyses highlight the importance of CNEs in gene regulation associated with the development of hermaphrodites.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adn9913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231176","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}
Dinghao Chen, Ziao Zhou, Nan Kong, Tengyan Xu, Juan Liang, Pingping Xu, Bingpeng Yao, Yu Zhang, Ying Sun, Ying Li, Bihan Wu, Xuejiao Yang, Huaimin Wang
Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.
革兰氏阴性菌（GNB）诱发的急性肺泡炎症会导致呼吸衰竭，而目前的药物治疗仍然徒劳无益。抗生素治疗后脂质多糖的释放以及随后促炎级联反应的进展，突出表明了同时应用有效炎症管理的必要性。这项研究介绍了用于快速抗炎编程的模块化自组装肽（SPRAY），它能形成专门针对巨噬细胞的纳米颗粒，同时具有抗炎和杀菌功能。SPRAY 纳米粒子通过溶酶体膜渗透加速巨噬细胞的自我递送过程，维持巨噬细胞的抗炎程序，其功效接近 T 辅助 2 细胞因子。通过肺沉积，SPRAY 纳米粒子能有效抑制炎症浸润，促进小鼠无菌性急性肺损伤的肺泡再生。此外，SPRAY 纳米粒子还能通过破坏细菌膜有效清除肺泡中的耐多药 GNB。SPRAY 纳米粒子的通用分子设计为逆转以促炎症细胞和耐药细菌高度聚集为特征的急性炎症提供了一种稳健且临床上未见的局部策略。
{"title":"Inhalable SPRAY nanoparticles by modular peptide assemblies reverse alveolar inflammation in lethal Gram-negative bacteria infection","authors":"Dinghao Chen, Ziao Zhou, Nan Kong, Tengyan Xu, Juan Liang, Pingping Xu, Bingpeng Yao, Yu Zhang, Ying Sun, Ying Li, Bihan Wu, Xuejiao Yang, Huaimin Wang","doi":"10.1126/sciadv.ado1749","DOIUrl":"10.1126/sciadv.ado1749","url":null,"abstract":"<div >Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado1749","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231174","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}
Today’s high-choice digital media environments allow citizens to completely refrain from online news exposure and, if they do use news, to select sources that align with their ideological preferences. Yet due to measurement problems and cross-country differences, recent research has been inconclusive regarding the prevalence of ideological self-selection into like-minded online news. We introduce a multi-method design combining the web-browsing histories and survey responses of more than 7000 participants from six major democracies with supervised text classification to separate political from nonpolitical news exposure. We find that political online news exposure is both substantially less prevalent and subject to stronger ideological self-selection than nonpolitical online news exposure, especially in the United States. By highlighting the peculiar role of political news content, the results improve the understanding of online news exposure and the role of digital media in democracy.
{"title":"Ideological self-selection in online news exposure: Evidence from Europe and the US","authors":"Frank Mangold, David Schoch, Sebastian Stier","doi":"10.1126/sciadv.adg9287","DOIUrl":"10.1126/sciadv.adg9287","url":null,"abstract":"<div >Today’s high-choice digital media environments allow citizens to completely refrain from online news exposure and, if they do use news, to select sources that align with their ideological preferences. Yet due to measurement problems and cross-country differences, recent research has been inconclusive regarding the prevalence of ideological self-selection into like-minded online news. We introduce a multi-method design combining the web-browsing histories and survey responses of more than 7000 participants from six major democracies with supervised text classification to separate political from nonpolitical news exposure. We find that political online news exposure is both substantially less prevalent and subject to stronger ideological self-selection than nonpolitical online news exposure, especially in the United States. By highlighting the peculiar role of political news content, the results improve the understanding of online news exposure and the role of digital media in democracy.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adg9287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231191","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}
Masato Fukumitsu, Tomoya Fukui, Yoshiaki Shoji, Takashi Kajitani, Ramsha Khan, Nikolai V. Tkachenko, Hayato Sakai, Taku Hasobe, Takanori Fukushima
Molecular assemblies featuring two-dimensionality have attracted increasing attention, whereas such structures are difficult to construct simply relying on spontaneous molecular assembly. Here, we present two-dimensional assemblies of acene chromophores achieved using a tripodal triptycene supramolecular scaffold, which have been shown to exhibit a strong ability to assemble molecular and polymer motifs two-dimensionally. We designed pentacene and anthracene derivatives sandwiched by two triptycene units. These compounds assemble into expected two-dimensional structures, with the pentacene chromophores having both sufficient overlap to cause singlet fission and space for conformational change to facilitate the dissociation of a triplet pair into free triplets, which is not the case for the anthracene analog. Detailed spectroscopic analysis revealed that the pentacene chromophore in the assembly undergoes singlet fission with a quantum yield of 88 ± 5%, giving rise to triplet pairs, from which free triplets are efficiently generated (ΦT = 130 ± 8.8%). This demonstrates the utility of the triptycene-based scaffold to design functional π-electronic molecular assemblies.
{"title":"Supramolecular scaffold–directed two-dimensional assembly of pentacene into a configuration to facilitate singlet fission","authors":"Masato Fukumitsu, Tomoya Fukui, Yoshiaki Shoji, Takashi Kajitani, Ramsha Khan, Nikolai V. Tkachenko, Hayato Sakai, Taku Hasobe, Takanori Fukushima","doi":"10.1126/sciadv.adn7763","DOIUrl":"10.1126/sciadv.adn7763","url":null,"abstract":"<div >Molecular assemblies featuring two-dimensionality have attracted increasing attention, whereas such structures are difficult to construct simply relying on spontaneous molecular assembly. Here, we present two-dimensional assemblies of acene chromophores achieved using a tripodal triptycene supramolecular scaffold, which have been shown to exhibit a strong ability to assemble molecular and polymer motifs two-dimensionally. We designed pentacene and anthracene derivatives sandwiched by two triptycene units. These compounds assemble into expected two-dimensional structures, with the pentacene chromophores having both sufficient overlap to cause singlet fission and space for conformational change to facilitate the dissociation of a triplet pair into free triplets, which is not the case for the anthracene analog. Detailed spectroscopic analysis revealed that the pentacene chromophore in the assembly undergoes singlet fission with a quantum yield of 88 ± 5%, giving rise to triplet pairs, from which free triplets are efficiently generated (Φ<sub>T</sub> = 130 ± 8.8%). This demonstrates the utility of the triptycene-based scaffold to design functional π-electronic molecular assemblies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adn7763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231189","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}
Paweł Moskal, Jakub Baran, Steven Bass, Jarosław Choiński, Neha Chug, Catalina Curceanu, Eryk Czerwiński, Meysam Dadgar, Manish Das, Kamil Dulski, Kavya V. Eliyan, Katarzyna Fronczewska, Aleksander Gajos, Krzysztof Kacprzak, Marcin Kajetanowicz, Tevfik Kaplanoglu, Łukasz Kapłon, Konrad Klimaszewski, Małgorzata Kobylecka, Grzegorz Korcyl, Tomasz Kozik, Wojciech Krzemień, Karol Kubat, Deepak Kumar, Jolanta Kunikowska, Joanna Mączewska, Wojciech Migdał, Gabriel Moskal, Wiktor Mryka, Szymon Niedźwiecki, Szymon Parzych, Elena P. del Rio, Lech Raczyński, Sushil Sharma, Shivani Shivani, Roman Y. Shopa, Michał Silarski, Magdalena Skurzok, Faranak Tayefi, Keyvan T. Ardebili, Pooja Tanty, Wojciech Wiślicki, Leszek Królicki, Ewa Ł. Stępień
Positronium is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo.
在正电子发射断层扫描（PET）过程中，病人体内的分子空隙中会大量产生正电子。它的特性会随着组织的亚分子结构和氧分压的变化而变化。目前的 PET 系统只能记录两个湮灭光子，无法提供有关正电子寿命的信息。这项研究利用专用的雅盖隆 PET 系统，同时检测放射性核素发射的湮灭光子和瞬时伽马射线，为胶质母细胞瘤脑瘤患者提供了正电子寿命的活体图像。瞬发伽马能提供正电子形成时间的信息。正电子湮灭产生的光子可用于重建其衰变的地点和时间。在本案例研究中，所测定的胶质母细胞瘤细胞中的正电子和正电子寿命比唾液腺和健康脑组织中的正电子和正电子寿命短，这表明正电子成像可用于体内疾病诊断。
{"title":"Positronium image of the human brain in vivo","authors":"Paweł Moskal, Jakub Baran, Steven Bass, Jarosław Choiński, Neha Chug, Catalina Curceanu, Eryk Czerwiński, Meysam Dadgar, Manish Das, Kamil Dulski, Kavya V. Eliyan, Katarzyna Fronczewska, Aleksander Gajos, Krzysztof Kacprzak, Marcin Kajetanowicz, Tevfik Kaplanoglu, Łukasz Kapłon, Konrad Klimaszewski, Małgorzata Kobylecka, Grzegorz Korcyl, Tomasz Kozik, Wojciech Krzemień, Karol Kubat, Deepak Kumar, Jolanta Kunikowska, Joanna Mączewska, Wojciech Migdał, Gabriel Moskal, Wiktor Mryka, Szymon Niedźwiecki, Szymon Parzych, Elena P. del Rio, Lech Raczyński, Sushil Sharma, Shivani Shivani, Roman Y. Shopa, Michał Silarski, Magdalena Skurzok, Faranak Tayefi, Keyvan T. Ardebili, Pooja Tanty, Wojciech Wiślicki, Leszek Królicki, Ewa Ł. Stępień","doi":"10.1126/sciadv.adp2840","DOIUrl":"10.1126/sciadv.adp2840","url":null,"abstract":"<div >Positronium is abundantly produced within the molecular voids of a patient’s body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp2840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231180","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}
Martina Begnis, Julien Duc, Sandra Offner, Delphine Grun, Shaoline Sheppard, Olga Rosspopoff, Didier Trono
Long known as the site of ribosome biogenesis, the nucleolus is increasingly recognized for its role in shaping three-dimensional (3D) genome organization. Still, the mechanisms governing the targeting of selected regions of the genome to nucleolus-associated domains (NADs) remain enigmatic. Here, we reveal the essential role of ZNF274, a SCAN-bearing member of the Krüppel-associated box (KRAB)–containing zinc finger protein (KZFP) family, in sequestering lineage-specific gene clusters within NADs. Ablation of ZNF274 triggers transcriptional activation across entire genomic neighborhoods—encompassing, among others, protocadherin and KZFP-encoding genes—with loss of repressive chromatin marks, altered the 3D genome architecture and de novo CTCF binding. Mechanistically, ZNF274 anchors target DNA sequences at the nucleolus and facilitates their compartmentalization via a previously uncharted function of the SCAN domain. Our findings illuminate the mechanisms underlying NAD organization and suggest that perinucleolar entrapment into repressive hubs constrains the activation of tandemly arrayed genes to enable selective expression and modulate cell differentiation programs during development.
核仁长期以来被称为核糖体生物发生的场所，其在塑造三维（3D）基因组组织方面的作用也日益得到认可。然而，基因组选定区域靶向核仁相关结构域（NADs）的机制仍然是个谜。在这里，我们揭示了ZNF274在NADs内隔离谱系特异性基因簇的重要作用，ZNF274是含锌指蛋白（KZFP）家族中的一个SCAN成员。消减 ZNF274 会引发整个基因组邻域的转录激活--其中包括原粘连蛋白和 KZFP 编码基因--抑制性染色质标记的缺失、三维基因组结构的改变以及新的 CTCF 结合。从机理上讲，ZNF274 将目标 DNA 序列锚定在核仁上，并通过 SCAN 结构域以前未知的功能促进其分隔。我们的研究结果阐明了 NAD 组织的基本机制，并表明核仁周围的抑制性中枢限制了串联排列基因的激活，从而在发育过程中实现选择性表达并调节细胞分化程序。
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Hannah S. Kenagy, Colette L. Heald, Nadia Tahsini, Matthew B. Goss, Jesse H. Kroll
Secondary organic aerosol (SOA), atmospheric particulate matter formed from low-volatility products of volatile organic compound (VOC) oxidation, affects both air quality and climate. Current 3D models, however, cannot reproduce the observed variability in atmospheric organic aerosol. Because many SOA model descriptions are derived from environmental chamber experiments, our ability to represent atmospheric conditions in chambers directly affects our ability to assess the air quality and climate impacts of SOA. Here, we develop an approach that leverages global modeling and detailed mechanisms to design chamber experiments that mimic the atmospheric chemistry of organic peroxy radicals (RO2), a key intermediate in VOC oxidation. Drawing on decades of laboratory experiments, we develop a framework for quantitatively describing RO2 chemistry and show that no previous experimental approaches to studying SOA formation have accessed the relevant atmospheric RO2 fate distribution. We show proof-of-concept experiments that demonstrate how SOA experiments can access a range of atmospheric chemical environments and propose several directions for future studies.
二次有机气溶胶（SOA）是由挥发性有机化合物（VOC）氧化的低挥发性产物形成的大气颗粒物，对空气质量和气候都有影响。然而，目前的三维模型无法再现观测到的大气有机气溶胶的变化。由于许多 SOA 模型描述都来自环境试验室实验，因此我们在试验室中表现大气条件的能力直接影响到我们评估 SOA 对空气质量和气候影响的能力。在这里，我们开发了一种方法，利用全球建模和详细机制来设计模拟有机过氧自由基（RO2）大气化学性质的室内实验，RO2 是挥发性有机化合物氧化过程中的一个关键中间产物。借鉴数十年的实验室实验，我们建立了一个定量描述 RO2 化学性质的框架，并证明以前研究 SOA 形成的实验方法都无法获得相关的大气 RO2 归宿分布。我们展示了概念验证实验，证明了 SOA 实验如何能够进入一系列大气化学环境，并提出了未来研究的几个方向。
{"title":"Can we achieve atmospheric chemical environments in the laboratory? An integrated model-measurement approach to chamber SOA studies","authors":"Hannah S. Kenagy, Colette L. Heald, Nadia Tahsini, Matthew B. Goss, Jesse H. Kroll","doi":"10.1126/sciadv.ado1482","DOIUrl":"10.1126/sciadv.ado1482","url":null,"abstract":"<div >Secondary organic aerosol (SOA), atmospheric particulate matter formed from low-volatility products of volatile organic compound (VOC) oxidation, affects both air quality and climate. Current 3D models, however, cannot reproduce the observed variability in atmospheric organic aerosol. Because many SOA model descriptions are derived from environmental chamber experiments, our ability to represent atmospheric conditions in chambers directly affects our ability to assess the air quality and climate impacts of SOA. Here, we develop an approach that leverages global modeling and detailed mechanisms to design chamber experiments that mimic the atmospheric chemistry of organic peroxy radicals (RO<sub>2</sub>), a key intermediate in VOC oxidation. Drawing on decades of laboratory experiments, we develop a framework for quantitatively describing RO<sub>2</sub> chemistry and show that no previous experimental approaches to studying SOA formation have accessed the relevant atmospheric RO<sub>2</sub> fate distribution. We show proof-of-concept experiments that demonstrate how SOA experiments can access a range of atmospheric chemical environments and propose several directions for future studies.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ado1482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231188","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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