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The path to condensates—19th Wiley Prize in Biomedical Sciences laureates share their discovery stories 凝聚之路——第19届威利生物医学科学奖得主分享他们的发现故事
Pub Date : 2022-10-02 DOI: 10.1002/ntls.20210091
C. Brangwynne, A. Hyman, M. Rosen
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引用次数: 0
Rational Design for High Bioorthogonal Fluorogenicity of Tetrazine-Encoded Green Fluorescent Proteins. 四嗪编码绿色荧光蛋白高生物正交荧光性的合理设计。
Pub Date : 2022-10-01 Epub Date: 2022-08-08 DOI: 10.1002/ntls.20220028
Longteng Tang, Riley M Bednar, Nikita D Rozanov, Marcus L Hemshorn, Ryan A Mehl, Chong Fang

The development of bioorthogonal fluorogenic probes constitutes a vital force to advance life sciences. Tetrazine-encoded green fluorescent proteins (GFPs) show high bioorthogonal reaction rate and genetic encodability, but suffer from low fluorogenicity. Here, we unveil the real-time fluorescence mechanisms by investigating two site-specific tetrazine-modified superfolder GFPs via ultrafast spectroscopy and theoretical calculations. Förster resonance energy transfer (FRET) is quantitatively modeled and revealed to govern the fluorescence quenching; for GFP150-Tet with a fluorescence turn-on ratio of ~9, it contains trimodal subpopulations with good (P1), random (P2), and poor (P3) alignments between the transition dipole moments of protein chromophore (donor) and tetrazine tag (Tet-v2.0, acceptor). By rationally designing a more free/tight environment, we created new mutants Y200A/S202Y to introduce more P2/P1 populations and improve the turn-on ratios to ~14/31, making the fluorogenicity of GFP150-Tet-S202Y the highest among all up-to-date tetrazine-encoded GFPs. In live eukaryotic cells, the GFP150-Tet-v3.0-S202Y mutant demonstrates notably increased fluorogenicity, substantiating our generalizable design strategy.

生物正交荧光探针的开发是推动生命科学发展的重要力量。四嗪编码的绿色荧光蛋白(GFP)显示出高的生物正交反应速率和遗传可编码性,但具有低的荧光原性。在这里,我们通过超快光谱和理论计算研究了两种位点特异的四嗪修饰的超折叠GFP,揭示了实时荧光机制。对Förster共振能量转移(FRET)进行了定量建模,并揭示了其对荧光猝灭的控制作用;对于荧光开启率为~9的GFP150 Tet,它包含蛋白质发色团(供体)和四嗪标签(Tet-v2.0,受体)的过渡偶极矩之间具有良好(P1)、随机(P2)和较差(P3)排列的三峰亚群。通过合理设计一个更自由/更紧密的环境,我们创造了新的突变体Y200A/S202Y,以引入更多的P2/P1群体,并将开启率提高到~14/31,使GFP150-Tet-S202Y的荧光原性在所有最新的四嗪编码的GFP中最高。在活的真核细胞中,GFP150-Tet-v3.0-S202Y突变体表现出显著增加的荧光原性,证实了我们的可推广设计策略。
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引用次数: 4
Diverse roles for axon guidance pathways in adult tissue architecture and function. 轴突引导通路在成人组织结构和功能中的不同作用。
Pub Date : 2022-10-01 Epub Date: 2022-10-02 DOI: 10.1002/ntls.20220021
Kaitlin M Laws, Greg J Bashaw

Classical axon guidance ligands and their neuronal receptors were first identified due to their fundamental roles in regulating connectivity in the developing nervous system. Since their initial discovery, it has become clear that these signaling molecules play important roles in the development of a broad array of tissue and organ systems across phylogeny. In addition to these diverse developmental roles, there is a growing appreciation that guidance signaling pathways have important functions in adult organisms, including the regulation of tissue integrity and homeostasis. These roles in adult organisms include both tissue-intrinsic activities of guidance molecules, as well as systemic effects on tissue maintenance and function mediated by the nervous and vascular systems. While many of these adult functions depend on mechanisms that mirror developmental activities, such as regulating adhesion and cell motility, there are also examples of adult roles that may reflect signaling activities that are distinct from known developmental mechanisms, including the contributions of guidance signaling pathways to lineage commitment in the intestinal epithelium and bone remodeling in vertebrates. In this review, we highlight studies of guidance receptors and their ligands in adult tissues outside of the nervous system, focusing on in vivo experimental contexts. Together, these studies lay the groundwork for future investigation into the conserved and tissue-specific mechanisms of guidance receptor signaling in adult tissues.

经典的轴突引导配体及其神经元受体因其在发育中的神经系统中调节连接的基本作用而首次被鉴定。自从它们最初被发现以来,很明显,这些信号分子在系统发育中的广泛组织和器官系统的发展中发挥着重要作用。除了这些不同的发育作用外,人们越来越认识到引导信号通路在成年生物体中具有重要功能,包括调节组织完整性和稳态。这些在成年生物体中的作用包括引导分子的组织内在活性,以及神经和血管系统介导的对组织维持和功能的系统性影响。虽然这些成人功能中的许多依赖于反映发育活动的机制,如调节粘附和细胞运动,但也有成人作用的例子可能反映不同于已知发育机制的信号活动,包括指导信号通路对脊椎动物肠上皮谱系承诺和骨重塑的贡献。在这篇综述中,我们重点介绍了神经系统外成人组织中引导受体及其配体的研究,重点是体内实验环境。这些研究共同为未来研究成人组织中引导受体信号传导的保守和组织特异性机制奠定了基础。
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引用次数: 1
Scents from the past: Lineage history and terminal identity in the olfactory system. 来自过去的气味:嗅觉系统的血统历史和终端身份。
Pub Date : 2022-10-01 DOI: 10.1002/ntls.20220037
Sriivatsan G Rajan, Ankur Saxena
The development of the vertebrate nose depends upon the interaction and intermingling of multiple progenitor subtypes, giving rise to olfactory epithelia that detect sensory information and transmit it to the brain.1,2 The olfactory epithelium is a dense and complex structure that houses numerous specialized cell types, including olfactory sensory neurons (OSNs) and, additionally, is thought to be the origin of migratory gonadotropin-releasing hormone (GnRH) neurons.2–4
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引用次数: 0
Singlet‐exciton optics and phonon‐mediated dynamics in oligoacene semiconductor crystals 寡聚丙烯酸半导体晶体中的单线态激子光学和声子介导动力学
Pub Date : 2022-09-12 DOI: 10.1002/ntls.20220040
J. Thompson, D. Muth, Sebastian Anhäuser, D. Bischof, M. Gerhard, G. Witte, E. Malic
Organic semiconductor crystals stand out as an efficient, cheap and diverse platform for realising optoelectronic applications. The optical response of these crystals is governed by a rich tapestry of exciton physics. So far, little is known on the phonon-driven singlet exciton dynamics in this class of materials. In this joint theory-experiment work, we combine the fabrication of a high-quality oligoacene semiconductor crystal and characterization via photoluminescence measurements with a sophisticated approach to the microscopic modeling in these crystals. This allows us to investigate singlet exciton optics and dynamics. We predict phonon-bottleneck effects in pentacene crystals, where we find dark excitons acting as crucial phonon-mediated relaxation scattering channels. While the efficient singlet fission in pentacene crystals hampers the experimental observation of this bottleneck effect, we reveal both in theory and experiment a distinct polarisation- and temperature-dependence in absorption and photoluminescence spectra of tetracene crystals, including microscopic origin of exciton linewidths, the activation of the higher Davydov states at large temperatures, and polarisation-dependent quenching of specific exciton resonances. Our joint theory-experiment study represents a significant advance in microscopic understanding of singlet exciton optics and dynamics in oligoacene crystals.
有机半导体晶体是实现光电应用的高效、廉价和多样化的平台。这些晶体的光学响应是由丰富的激子物理学所控制的。到目前为止,对这类材料中声子驱动的单重态激子动力学知之甚少。在这项理论-实验联合工作中,我们结合了高质量低聚丙烯酸半导体晶体的制造和通过光致发光测量的表征,并采用了一种复杂的方法来对这些晶体进行微观建模。这允许我们研究单线态激子光学和动力学。我们预测了并五苯晶体中的声子瓶颈效应,在那里我们发现暗激子作为关键的声子介导的弛豫散射通道。虽然并五烯晶体中有效的单线态裂变阻碍了这种瓶颈效应的实验观察,但我们在理论和实验中都揭示了四烯晶体吸收和光致发光光谱中明显的极化和温度依赖性,包括激子线宽的微观起源,高达维多夫态在高温下的激活,以及特定激子共振的极化依赖性猝灭。我们的理论-实验联合研究代表了对少聚丙烯酸晶体中单线态激子光学和动力学的微观理解的重大进展。
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引用次数: 2
The impact of optical excitation on the binding in complexes of the cationic gold dimer: Au2+N2${rm{Au}_{2}^{+}} {rm{N}_{2}} $ and Au2+N2O${rm{Au}_{2}^{+}} {rm{N}_{2}{rm{O}}} $ 光激发对阳离子金二聚体配合物结合的影响:Au2+N2${rm{Au}_{2}}^{+}} {rm{N}_{2}}和Au2+N2O${rm{Au}_{2}}} {rm{O}}} $
Pub Date : 2022-08-19 DOI: 10.1002/ntls.20220023
M. Förstel, Nima‐Noah Nahvi, Kai Pollow, T. Studemund, Alice E. Green, A. Fielicke, S. Mackenzie, O. Dopfer
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引用次数: 0
Convolutional neural network prediction of molecular properties for aerosol chemistry and health effects 卷积神经网络预测气溶胶化学和健康影响的分子特性
Pub Date : 2022-08-18 DOI: 10.1002/ntls.20220016
Matteo Krüger, Jake Wilson, M. Wietzoreck, B. A. Bandowe, G. Lammel, B. Schmidt, U. Pöschl, T. Berkemeier
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引用次数: 4
2D/0D hierarchical heterostructures prepared via facet‐selective epitaxial growth of triangular Rh nanoplates on 2H‐Pd nanoparticles 三角形Rh纳米片在2H - Pd纳米颗粒表面选择性外延生长制备2D/0D分层异质结构
Pub Date : 2022-08-11 DOI: 10.1002/ntls.20220026
Xixi Wang, Yiyao Ge, Qinghua Zhang, Ting Lin, Bo Chen, Lujiang Li, Zhiqi Huang, Qinbai Yun, Xichen Zhou, Zhenyu Shi, Guanghua Liu, Jiawei Liu, G. Wang, Long Zheng, B. Huang, Lingwen Liao, Yao Yao, Liying Zhai, Shiyao Lu, Qinxin Luo, Yenying W. Chen, Lin Gu, Hua Zhang
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引用次数: 1
The road toward imaging a black hole: A personal perspective 黑洞成像之路:个人视角
Pub Date : 2022-08-01 DOI: 10.1002/ntls.20220031
H. Falcke
The images of the supermassive black holes Sgr A* and M87* by the Event Horizon Telescope (EHT) collaboration mark a special milestone in the history of the subject. For the first time we are able to see the shadow of black holes, testing basic predictions of the theory of general relativity. We are also now learning more about the fundamental astrophysical processes close to the event horizon that help to shape entire galaxies and even parts of our cosmos. The ultimate result was only possible due to a large collaborative effort of scientists and institutions around the world. The road towards these images was the result of a long sociological and scientific process. It started with early pathfinder experiments and a few simple ideas that were remarkably successful in predicting the basic observational signatures to look for. This was based on the premise that black holes are inherently simple objects. Here I describe this journey and some lessons learned from a personal perspective.
事件视界望远镜(EHT)合作拍摄的超大质量黑洞Sgr A*和M87*的图像标志着该学科历史上一个特殊的里程碑。我们第一次能够看到黑洞的阴影,验证广义相对论的基本预测。我们现在也在更多地了解事件视界附近的基本天体物理过程,这些过程有助于塑造整个星系,甚至是我们宇宙的一部分。由于世界各地的科学家和机构的大量合作努力,最终的结果才有可能实现。通往这些图像的道路是一个长期的社会学和科学过程的结果。它从早期的探路者实验和一些简单的想法开始,这些想法在预测要寻找的基本观测特征方面非常成功。这是基于黑洞本质上是简单物体的前提。在这里,我将从个人角度描述这段旅程和一些经验教训。
{"title":"The road toward imaging a black hole: A personal perspective","authors":"H. Falcke","doi":"10.1002/ntls.20220031","DOIUrl":"https://doi.org/10.1002/ntls.20220031","url":null,"abstract":"The images of the supermassive black holes Sgr A* and M87* by the Event Horizon Telescope (EHT) collaboration mark a special milestone in the history of the subject. For the first time we are able to see the shadow of black holes, testing basic predictions of the theory of general relativity. We are also now learning more about the fundamental astrophysical processes close to the event horizon that help to shape entire galaxies and even parts of our cosmos. The ultimate result was only possible due to a large collaborative effort of scientists and institutions around the world. The road towards these images was the result of a long sociological and scientific process. It started with early pathfinder experiments and a few simple ideas that were remarkably successful in predicting the basic observational signatures to look for. This was based on the premise that black holes are inherently simple objects. Here I describe this journey and some lessons learned from a personal perspective.","PeriodicalId":74244,"journal":{"name":"Natural sciences (Weinheim, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90428995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Multimodal imaging reveals a small subpopulation of Deinococcus radiodurans exhibiting correlated low superoxide radical levels with extraordinary silver ion metabolism 多模态成像显示耐辐射球菌小亚群表现出与异常银离子代谢相关的低超氧自由基水平
Pub Date : 2022-07-28 DOI: 10.1002/ntls.20210507
Wei Zhu, Xinyu He, Haoran Li, Bo Jiang, Ruochen Xie, Wei Wang
{"title":"Multimodal imaging reveals a small subpopulation of\u0000 Deinococcus radiodurans\u0000 exhibiting correlated low superoxide radical levels with extraordinary silver ion metabolism","authors":"Wei Zhu, Xinyu He, Haoran Li, Bo Jiang, Ruochen Xie, Wei Wang","doi":"10.1002/ntls.20210507","DOIUrl":"https://doi.org/10.1002/ntls.20210507","url":null,"abstract":"","PeriodicalId":74244,"journal":{"name":"Natural sciences (Weinheim, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81364860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Natural sciences (Weinheim, Germany)
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