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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.


  
Structural basis of receptor recognition by SARS-CoV-2 期刊论文
NATURE, 2020, 581 (7807) : 221-+
作者:  Ehrenreich, David;  39;Odorico, Valentina
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19(1,2). A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans(3,4). Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation  moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.


  
A mechanism of ferritin crystallization revealed by cryo-STEM tomography 期刊论文
NATURE, 2020, 579 (7800) : 540-+
作者:  van Gastel, Nick;  Stegen, Steve;  Eelen, Guy;  Schoors, Sandra;  Carlier, Aurelie;  Daniels, Veerle W.;  Baryawno, Ninib;  Przybylski, Dariusz;  Depypere, Maarten;  Stiers, Pieter-Jan;  Lambrechts, Dennis;  Van Looveren, Riet;  Torrekens, Sophie
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Protein crystallization is important in structural biology, disease research and pharmaceuticals. It has recently been recognized that nonclassical crystallization involving initial formation of an amorphous precursor phase-occurs often in protein, organic and inorganic crystallization processes(1-5). A two-step nucleation theory has thus been proposed, in which initial low-density, solvated amorphous aggregates subsequently densify, leading to nucleation(4,6,7). This view differs from classical nucleation theory, which implies that crystalline nuclei forming in solution have the same density and structure as does the final crystalline state(1). A protein crystallization mechanism involving this classical pathway has recently been observed directly(8). However, a molecular mechanism of nonclassical protein crystallization(9-15) has not been established(9,11,14). To determine the nature of the amorphous precursors and whether crystallization takes place within them (and if so, how order develops at the molecular level), three-dimensional (3D) molecular-level imaging of a crystallization process is required. Here we report cryogenic scanning transmission microscopy tomography of ferritin aggregates at various stages of crystallization, followed by 3D reconstruction using simultaneous iterative reconstruction techniques to provide a 3D picture of crystallization with molecular resolution. As crystalline order gradually increased in the studied aggregates, they exhibited an increase in both order and density from their surface towards their interior. We observed no highly ordered small structures typical of a classical nucleation process, and occasionally we observed several ordered domains emerging within one amorphous aggregate, a phenomenon not predicted by either classical or two-step nucleation theories. Our molecular-level analysis hints at desolvation as the driver of the continuous order-evolution mechanism, a view that goes beyond current nucleation models, yet is consistent with a broad spectrum of protein crystallization mechanisms.


  
High-pressure strengthening in ultrafine-grained metals 期刊论文
NATURE, 2020
作者:  Yoshida, Kenichi;  Gowers, Kate H. C.;  Lee-Six, Henry;  Chandrasekharan, Deepak P.;  Coorens, Tim;  Maughan, Elizabeth F.;  Beal, Kathryn;  Menzies, Andrew;  Millar, Fraser R.;  Anderson, Elizabeth;  Clarke, Sarah E.;  Pennycuick, Adam;  Thakrar, Ricky M.;  Butler, Colin R.
收藏  |  浏览/下载:46/0  |  提交时间:2020/07/03

High-pressure diamond anvil cell experiments reveal that compression strengthening of nanocrystalline nickel increases as its grain sizes decrease to 3 nanometres, owing to dislocation hardening and suppression of grain boundary plasticity.


The Hall-Petch relationship, according to which the strength of a metal increases as the grain size decreases, has been reported to break down at a critical grain size of around 10 to 15 nanometres(1,2). As the grain size decreases beyond this point, the dominant mechanism of deformation switches from a dislocation-mediated process to grain boundary sliding, leading to material softening. In one previous approach, stabilization of grain boundaries through relaxation and molybdenum segregation was used to prevent this softening effect in nickel-molybdenum alloys with grain sizes below 10 nanometres(3). Here we track in situ the yield stress and deformation texturing of pure nickel samples of various average grain sizes using a diamond anvil cell coupled with radial X-ray diffraction. Our high-pressure experiments reveal continuous strengthening in samples with grain sizes from 200 nanometres down to 3 nanometres, with the strengthening enhanced (rather than reduced) at grain sizes smaller than 20 nanometres. We achieve a yield strength of approximately 4.2 gigapascals in our 3-nanometre-grain-size samples, ten times stronger than that of a commercial nickel material. A maximum flow stress of 10.2 gigapascals is obtained in nickel of grain size 3 nanometres for the pressure range studied here. We see similar patterns of compression strengthening in gold and palladium samples down to the smallest grain sizes. Simulations and transmission electron microscopy reveal that the high strength observed in nickel of grain size 3 nanometres is caused by the superposition of strengthening mechanisms: both partial and full dislocation hardening plus suppression of grain boundary plasticity. These insights contribute to the ongoing search for ultrastrong metals via materials engineering.


  
Li metal deposition and stripping in a solid-state battery via Coble creep 期刊论文
NATURE, 2020, 578 (7794) : 251-+
作者:  Helmrich, S.;  Arias, A.;  Lochead, G.;  Wintermantel, T. M.;  Buchhold, M.;  Diehl, S.;  Whitlock, S.
收藏  |  浏览/下载:68/0  |  提交时间:2020/07/03

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be(1,2) up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 10(10) MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1x excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.


By containing lithium metal within oriented tubes of a mixed ionic-electronic conductor, a 3D anode for lithium metal batteries is produced that overcomes chemomechanical stability issues at the electrolyte interface.


  
Transmission mechanism between energy prices and carbon emissions using geographically weighted regression 期刊论文
ENERGY POLICY, 2018, 115: 434-442
作者:  Li, Wei;  Sun, Wen;  Li, Guomin;  Jin, Baihui;  Wu, Wen;  Cui, Pengfei;  Zhao, Guohao
收藏  |  浏览/下载:17/0  |  提交时间:2019/04/09
Energy price  Carbon emissions  GWR Model  Transmission mechanism  
On economic inefficiency of European Inter-TSO compensation mechanism 期刊论文
ENERGY POLICY, 2017, 110
作者:  Sabolic, Dubravko
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09
Inter-Transmission System Operator Compensation (ITC) mechanism  EU electricity sector regulatory framework  Economic inefficiency of ITC mechanism  Correct reallocation