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A reaction chamber for chromatin modification 期刊论文
NATURE, 2020, 579 (7800) : 503-504
作者:  Inomata, Takeshi;  Triadan, Daniela;  Vazquez Lopez, Veronica A.;  Fernandez-Diaz, Juan Carlos;  Omori, Takayuki;  Mendez Bauer, Maria Belen;  Garcia Hernandez, Melina;  Beach, Timothy;  Cagnato, Clarissa;  Aoyama, Kazuo;  Nasu, Hiroo
收藏  |  浏览/下载:20/0  |  提交时间:2020/07/03

Chromatin, the complex of DNA and protein in cell nuclei, can be modified by ubiquitin molecules. It emerges that this modification occurs in a molecular reaction chamber formed from an enzyme and a scaffold protein.


A phase-separated reaction chamber for chromatin ubiquitination.


  
Coupling delay controls synchronized oscillation in the segmentation clock 期刊论文
NATURE, 2020
作者:  Yoshioka-Kobayashi, Kumiko;  Matsumiya, Marina;  Niino, Yusuke;  Isomura, Akihiro;  Kori, Hiroshi;  Miyawaki, Atsushi;  Kageyama, Ryoichiro
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Individual cellular activities fluctuate but are constantly coordinated at the population level via cell-cell coupling. A notable example is the somite segmentation clock, in which the expression of clock genes (such as Hes7) oscillates in synchrony between the cells that comprise the presomitic mesoderm (PSM)(1,2). This synchronization depends on the Notch signalling pathway  inhibiting this pathway desynchronizes oscillations, leading to somite fusion(3-7). However, how Notch signalling regulates the synchronicity of HES7 oscillations is unknown. Here we establish a live-imaging system using a new fluorescent reporter (Achilles), which we fuse with HES7 to monitor synchronous oscillations in HES7 expression in the mouse PSM at a single-cell resolution. Wild-type cells can rapidly correct for phase fluctuations in HES7 oscillations, whereas the absence of the Notch modulator gene lunatic fringe (Lfng) leads to a loss of synchrony between PSM cells. Furthermore, HES7 oscillations are severely dampened in individual cells of Lfng-null PSM. However, when Lfng-null PSM cells were completely dissociated, the amplitude and periodicity of HES7 oscillations were almost normal, which suggests that LFNG is involved mostly in cell-cell coupling. Mixed cultures of control and Lfng-null PSM cells, and an optogenetic Notch signalling reporter assay, revealed that LFNG delays the signal-sending process of intercellular Notch signalling transmission. These results-together with mathematical modelling-raised the possibility that Lfng-null PSM cells shorten the coupling delay, thereby approaching a condition known as the oscillation or amplitude death of coupled oscillators(8). Indeed, a small compound that lengthens the coupling delay partially rescues the amplitude and synchrony of HES7 oscillations in Lfng-null PSM cells. Our study reveals a delay control mechanism of the oscillatory networks involved in somite segmentation, and indicates that intercellular coupling with the correct delay is essential for synchronized oscillation.


Monitoring cells of the mouse presomitic mesoderm using the Achilles reporter fused to HES7 sheds light on the mechanisms that underpin synchronous oscillations in the expression of clock genes between neighbouring cells.


  
Strain engineering and epitaxial stabilization of halide perovskites 期刊论文
NATURE, 2020, 577 (7789) : 209-+
作者:  Chen, Yimu;  Lei, Yusheng;  Li, Yuheng;  Yu, Yugang;  Cai, Jinze;  Chiu, Ming-Hui;  Rao, Rahul;  Gu, Yue;  Wang, Chunfeng;  Choi, Woojin;  Hu, Hongjie;  Wang, Chonghe;  Li, Yang;  Song, Jiawei;  Zhang, Jingxin;  Qi, Baiyan;  Lin, Muyang;  Zhang, Zhuorui;  Islam, Ahmad E.;  Maruyama, Benji;  Dayeh, Shadi;  Li, Lain-Jong;  Yang, Kesong;  Lo, Yu-Hwa;  Xu, Sheng
收藏  |  浏览/下载:48/0  |  提交时间:2020/07/03

Strain engineering is a powerful tool with which to enhance semiconductor device performance(1,2). Halide perovskites have shown great promise in device applications owing to their remarkable electronic and optoelectronic properties(3-5). Although applying strain to halide perovskites has been frequently attempted, including using hydrostatic pressurization(6-8), electrostriction(9), annealing(10-12), van der Waals force(13), thermal expansion mismatch(14), and heat-induced substrate phase transition(15), the controllable and device-compatible strain engineering of halide perovskites by chemical epitaxy remains a challenge, owing to the absence of suitable lattice-mismatched epitaxial substrates. Here we report the strained epitaxial growth of halide perovskite single-crystal thin films on lattice-mismatched halide perovskite substrates. We investigated strain engineering of a-formamidinium lead iodide (alpha-FAPbI(3)) using both experimental techniques and theoretical calculations. By tailoring the substrate composition-and therefore its lattice parameter-a compressive strain as high as 2.4 per cent is applied to the epitaxial alpha-FAPbI(3) thin film. We demonstrate that this strain effectively changes the crystal structure, reduces the bandgap and increases the hole mobility of alpha-FAPbI(3). Strained epitaxy is also shown to have a substantial stabilization effect on the alpha-FAPbI(3) phase owing to the synergistic effects of epitaxial stabilization and strain neutralization. As an example, strain engineering is applied to enhance the performance of an alpha-FAPbI(3)-based photodetector.


  
Transparent ferroelectric crystals with ultrahigh piezoelectricity 期刊论文
NATURE, 2020, 577 (7790) : 350-+
作者:  Qiu, Chaorui;  Wang, Bo;  Zhang, Nan;  Zhang, Shujun;  Liu, Jinfeng;  Walker, David;  Wang, Yu;  Tian, Hao;  Shrout, Thomas R.;  Xu, Zhuo;  Chen, Long-Qing;  Li, Fei
收藏  |  浏览/下载:43/0  |  提交时间:2020/07/03

Transparent piezoelectrics are highly desirable for numerous hybrid ultrasound-optical devices ranging from photoacoustic imaging transducers to transparent actuators for haptic applications(1-7). However, it is challenging to achieve high piezoelectricity and perfect transparency simultaneously because most high-performance piezoelectrics are ferroelectrics that contain high-density light-scattering domain walls. Here, through a combination of phase-field simulations and experiments, we demonstrate a relatively simple method of using an alternating-current electric field to engineer the domain structures of originally opaque rhombohedral Pb(Mg1/3Nb2/3)O-3-PbTiO3 (PMN-PT) crystals to simultaneously generate near-perfect transparency, an ultrahigh piezoelectric coefficient d(33) (greater than 2,100 picocoulombs per newton), an excellent electromechanical coupling factor k(33) (about 94 per cent) and a large electro-optical coefficient gamma(33) (approximately 220 picometres per volt), which is far beyond the performance of the commonly used transparent ferroelectric crystal LiNbO3. We find that increasing the domain size leads to a higher d(33) value for the [001]-oriented rhombohedral PMN-PT crystals, challenging the conventional wisdom that decreasing the domain size always results in higher piezoelectricity(8-10). This work presents a paradigm for achieving high transparency and piezoelectricity by ferroelectric domain engineering, and we expect the transparent ferroelectric crystals reported here to provide a route to a wide range of hybrid device applications, such as medical imaging, self-energy-harvesting touch screens and invisible robotic devices.


  
Archimedean lattices emerge in template-directed eutectic solidification 期刊论文
NATURE, 2020, 577 (7790) : 355-+
作者:  Subbaraman, Nidhi;  Viglione, Giuliana
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

Template-directed assembly has been shown to yield a broad diversity of highly ordered mesostructures(1),(2), which in a few cases exhibit symmetries not present in the native material(3-5). However, this technique has not yet been applied to eutectic materials, which underpin many modern technologies ranging from high-performance turbine blades to solder alloys. Here we use directional solidification of a simple AgCl-KCl lamellar eutectic material within a pillar template to show that interactions of the material with the template lead to the emergence of a set of microstructures that are distinct from the eutectic'  s native lamellar structure and the template'  s hexagonal lattice structure. By modifying the solidification rate of this material-template system, trefoil, quatrefoil, cinquefoil and hexafoil mesostructures with submicrometre-size features are realized. Phase-field simulations suggest that these mesostructures appear owing to constraints imposed on diffusion by the hexagonally arrayed pillar template. We note that the trefoil and hexafoil patterns resemble Archimedean honeycomb and square-hexagonal-dodecagonal lattices(6), respectively. We also find that by using monolayer colloidal crystals as templates, a variety of eutectic mesostructures including trefoil and hexafoil are observed, the former resembling the Archimedean kagome lattice. Potential emerging applications for the structures provided by templated eutectics include non-reciprocal metasurfaces(7), magnetic spin-ice systems(8,9), and micro- and nano-lattices with enhanced mechanical properties(10,11).


  
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition 期刊论文
NATURE, 2020, 577 (7790) : 421-+
作者:  Xue, Jenny Y.;  Zhao, Yulei;  Aronowitz, Jordan;  Mai, Trang T.;  Vides, Alberto;  Qeriqi, Besnik;  Kim, Dongsung;  Li, Chuanchuan;  de Stanchina, Elisa;  Mazutis, Linas;  Risso, Davide;  Lito, Piro
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

KRAS GTPases are activated in one-third of cancers, and KRAS(G12C) is one of the most common activating alterations in lung adenocarcinoma(1,2). KRAS(G12C) inhibitors(3,4) are in phase-I clinical trials and early data show partial responses in nearly half of patients with lung cancer. How cancer cells bypass inhibition to prevent maximal response to therapy is not understood. Because KRAS(G12C) cycles between an active and inactive conformation(4-6), and the inhibitors bind only to the latter, we tested whether isogenic cell populations respond in a non-uniform manner by studying the effect of treatment at a single-cell resolution. Here we report that, shortly after treatment, some cancer cells are sequestered in a quiescent state with low KRAS activity, whereas others bypass this effect to resume proliferation. This rapid divergent response occurs because some quiescent cells produce new KRAS(G12C) in response to suppressed mitogen-activated protein kinase output. New KRAS(G12C) is maintained in its active, drug-insensitive state by epidermal growth factor receptor and aurora kinase signalling. Cells without these adaptive changes-or cells in which these changes are pharmacologically inhibited-remain sensitive to drug treatment, because new KRAS(G12C) is either not available or exists in its inactive, drug-sensitive state. The direct targeting of KRAS oncoproteins has been a longstanding objective in precision oncology. Our study uncovers a flexible non-uniform fitness mechanism that enables groups of cells within a population to rapidly bypass the effect of treatment. This adaptive process must be overcome if we are to achieve complete and durable responses in the clinic.


  
Rapid growth of new atmospheric particles by nitric acid and ammonia condensation 期刊论文
NATURE, 2020, 581 (7807) : 184-+
作者:  Liang, Guanxiang;  Zhao, Chunyu;  Zhang, Huanjia;  Mattei, Lisa;  Sherrill-Mix, Scott;  Bittinger, Kyle;  Kessler, Lyanna R.;  Wu, Gary D.;  Baldassano, Robert N.;  DeRusso, Patricia;  Ford, Eileen;  Elovitz, Michal A.;  Kelly, Matthew S.;  Patel, Mohamed Z.;  Mazhani, Tiny;  Gerber, Jeffrey S.;  Kelly, Andrea;  Zemel, Babette S.;  Bushman, Frederic D.
收藏  |  浏览/下载:41/0  |  提交时间:2020/05/20

A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog(1,2), but how it occurs in cities is often puzzling(3). If the growth rates of urban particles are similar to those found in cleaner environments (1-10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below -15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid-base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms(4,5).


  
Localization and delocalization of light in photonic moire lattices 期刊论文
NATURE, 2020, 577 (7788) : 42-+
作者:  Wang, Peng;  Zheng, Yuanlin;  Chen, Xianfeng;  Huang, Changming;  Kartashov, Yaroslav V.;  Torner, Lluis;  Konotop, Vladimir V.;  Ye, Fangwei
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Moire lattices consist of two superimposed identical periodic structures with a relative rotation angle. Moire lattices have several applications in everyday life, including artistic design, the textile industry, architecture, image processing, metrology and interferometry. For scientific studies, they have been produced using coupled graphene-hexagonal boron nitride monolayers(1,2), graphene-graphene layers(3,4) and graphene quasicrystals on a silicon carbide surface(5). The recent surge of interest in moire lattices arises from the possibility of exploring many salient physical phenomena in such systems  examples include commensurable-incommensurable transitions and topological defects(2), the emergence of insulating states owing to band flattening(3,6), unconventional superconductivity(4) controlled by the rotation angle(7,8), the quantum Hall effect(9), the realization of non-Abelian gauge potentials(10) and the appearance of quasicrystals at special rotation angles(11). A fundamental question that remains unexplored concerns the evolution of waves in the potentials defined by moire lattices. Here we experimentally create two-dimensional photonic moire lattices, which-unlike their material counterparts-have readily controllable parameters and symmetry, allowing us to explore transitions between structures with fundamentally different geometries (periodic, general aperiodic and quasicrystal). We observe localization of light in deterministic linear lattices that is based on flatband physics(6), in contrast to previous schemes based on light diffusion in optical quasicrystals(12), where disorder is required(13) for the onset of Anderson localization(14) (that is, wave localization in random media). Using commensurable and incommensurable moire patterns, we experimentally demonstrate the twodimensional localization-delocalization transition of light. Moire lattices may feature an almost arbitrary geometry that is consistent with the crystallographic symmetry groups of the sublattices, and therefore afford a powerful tool for controlling the properties of light patterns and exploring the physics of periodic-aperiodic phase transitions and two-dimensional wavepacket phenomena relevant to several areas of science, including optics, acoustics, condensed matter and atomic physics.


  
Potential circadian effects on translational failure for neuroprotection 期刊论文
NATURE, 2020
作者:  Sakai, Akito;  Minami, Susumu;  Koretsune, Takashi;  Chen, Taishi;  Higo, Tomoya;  Wang, Yangming;  Nomoto, Takuya;  Hirayama, Motoaki;  Miwa, Shinji;  Nishio-Hamane, Daisuke;  Ishii, Fumiyuki;  Arita, Ryotaro;  Nakatsuji, Satoru
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans(1,2) may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger alpha-phenyl-butyl-tert-nitrone (alpha PBN), and the N-methyl-d-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in '  active-phase'  than in '  inactive-phase'  rodent neurons. alpha PBN and MK801 reduced neuronal death only in '  inactive-phase'  neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.


Studies in rats and mice at different times of day suggest that the failure of neuroprotective strategies for stroke in translational studies might be related to the difference in circadian cycles between humans and rodents.


  
Mapping the twist-angle disorder and Landau levels in magic-angle graphene 期刊论文
NATURE, 2020, 581 (7806) : 47-+
作者:  Luck, Katja;  39;Amata, Cassandra
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG)(1,2) crucially depend on the interlayer twist angle, theta. Although control of the global theta with a precision of about 0.1 degrees has been demonstrated(1-7), little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip)(8) to obtain tomographic images of the Landau levels in the quantum Hall state(9) and to map the local theta variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moire periods. We find a correlation between the degree of theta disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in theta of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of theta generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of theta disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.


SQUID-on-tip tomographic imaging of Landau levels in magic-angle graphene provides nanoscale maps of local twist-angle disorder and shows that its properties are fundamentally different from common types of disorder.