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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:8/0  |  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.


  
Microbial bile acid metabolites modulate gut ROR gamma(+) regulatory T cell homeostasis 期刊论文
NATURE, 2020, 577 (7790) : 410-+
作者:  Bhargava, Manjul
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules(1). Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins(2). Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors(3,4). These receptors have pivotal roles in shaping host innate immune responses(1,5). However, the effect of this host-microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3(+) regulatory T (T-reg) cells expressing the transcription factor ROR gamma. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this T-reg cell population. Restoration of the intestinal BA pool increases colonic ROR gamma(+) T-reg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.


  
A neurotransmitter produced by gut bacteria modulates host sensory behaviour 期刊论文
NATURE, 2020
作者:  Zhao, Xiaoxu;  Song, Peng;  Wang, Chengcai;  Riis-Jensen, Anders C.;  Fu, Wei;  Deng, Ya;  Wan, Dongyang;  Kang, Lixing;  Ning, Shoucong;  Dan, Jiadong;  Venkatesan, T.;  Liu, Zheng;  Zhou, Wu;  Thygesen, Kristian S.;  Luo, Xin;  Pennycook, Stephen J.;  Loh, Kian Ping
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

A neuromodulator produced by commensalProvidenciabacteria that colonize the gut ofCaenorhabditis elegansmimics the functions of the cognate host molecule to manipulate a sensory decision of the host.


Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms(1). Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts(2,3). However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that inCaenorhabditis elegans, the neuromodulator tyramine produced by commensalProvidenciabacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine beta-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis inProvidencia, and show that these genes are necessary for the modulation of host behaviour. We further find thatC. eleganscolonized byProvidenciapreferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


  
Non-volatile electric control of spin-charge conversion in a SrTiO3 Rashba system 期刊论文
NATURE, 2020, 580 (7804) : 483-+
作者:  Collombet, Samuel;  Ranisavljevic, Noemie;  Nagano, Takashi;  Varnai, Csilla;  Shisode, Tarak;  Leung, Wing;  Piolot, Tristan;  Galupa, Rafael;  Borensztein, Maud;  Servant, Nicolas;  Fraser, Peter;  Ancelin, Katia;  Heard, Edith
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The polarization direction of a ferroelectric-like state can be used to control the conversion of spin currents into charge currents at the surface of strontium titanate, a non-magnetic oxide.


After 50 years of development, the technology of today'  s electronics is approaching its physical limits, with feature sizes smaller than 10 nanometres. It is also becoming clear that the ever-increasing power consumption of information and communication systems(1) needs to be contained. These two factors require the introduction of non-traditional materials and state variables. As recently highlighted(2), the remanence associated with collective switching in ferroic systems is an appealing way to reduce power consumption. A promising approach is spintronics, which relies on ferromagnets to provide non-volatility and to generate and detect spin currents(3). However, magnetization reversal by spin transfer torques(4) is a power-consuming process. This is driving research on multiferroics to achieve low-power electric-field control of magnetization(5), but practical materials are scarce and magnetoelectric switching remains difficult to control. Here we demonstrate an alternative strategy to achieve low-power spin detection, in a non-magnetic system. We harness the electric-field-induced ferroelectric-like state of strontium titanate (SrTiO3)(6-9) to manipulate the spin-orbit properties(10) of a two-dimensional electron gas(11), and efficiently convert spin currents into positive or negative charge currents, depending on the polarization direction. This non-volatile effect opens the way to the electric-field control of spin currents and to ultralow-power spintronics, in which non-volatility would be provided by ferroelectricity rather than by ferromagnetism.


  
Electrical manipulation of a topological antiferromagnetic state 期刊论文
NATURE, 2020, 580 (7805) : 608-+
作者:  Chabon, Jacob J.;  Hamilton, Emily G.;  Kurtz, David M.;  Esfahani, Mohammad S.;  Moding, Everett J.;  Stehr, Henning;  Schroers-Martin, Joseph;  Nabet, Barzin Y.;  Chen, Binbin;  Chaudhuri, Aadel A.;  Liu, Chih Long;  Hui, Angela B.;  Jin, Michael C.;  Azad, Tej D.;  Almanza, Diego;  Jeon, Young-Jun;  Nesselbush, Monica C.;  Keh, Lyron Co Ting;  Bonilla, Rene F.;  Yoo, Christopher H.;  Ko, Ryan B.;  Chen, Emily L.;  Merriott, David J.;  Massion, Pierre P.;  Mansfield, Aaron S.;  Jen, Jin;  Ren, Hong Z.;  Lin, Steven H.;  Costantino, Christina L.;  Burr, Risa;  Tibshirani, Robert;  Gambhir, Sanjiv S.;  Berry, Gerald J.;  Jensen, Kristin C.;  West, Robert B.;  Neal, Joel W.;  Wakelee, Heather A.;  Loo, Billy W., Jr.;  Kunder, Christian A.;  Leung, Ann N.;  Lui, Natalie S.;  Berry, Mark F.;  Shrager, Joseph B.;  Nair, Viswam S.;  Haber, Daniel A.;  Sequist, Lecia V.;  Alizadeh, Ash A.;  Diehn, Maximilian
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.


Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.


  
Operation of a silicon quantum processor unit cell above one kelvin 期刊论文
NATURE, 2020, 580 (7803) : 350-+
作者:  Han, Kyuho;  Pierce, Sarah E.;  Li, Amy;  Spees, Kaitlyn;  Anderson, Grace R.;  Seoane, Jose A.;  Lo, Yuan-Hung;  Dubreuil, Michael;  Olivas, Micah;  Kamber, Roarke A.;  Wainberg, Michael;  Kostyrko, Kaja;  Kelly, Marcus R.;  Yousefi, Maryam;  Simpkins, Scott W.;  Yao, David
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Quantum computers are expected to outperform conventional computers in several important applications, from molecular simulation to search algorithms, once they can be scaled up to large numbers-typically millions-of quantum bits (qubits)(1-3). For most solid-state qubit technologies-for example, those using superconducting circuits or semiconductor spins-scaling poses a considerable challenge because every additional qubit increases the heat generated, whereas the cooling power of dilution refrigerators is severely limited at their operating temperature (less than 100 millikelvin)(4-6). Here we demonstrate the operation of a scalable silicon quantum processor unit cell comprising two qubits confined to quantum dots at about 1.5 kelvin. We achieve this by isolating the quantum dots from the electron reservoir, and then initializing and reading the qubits solely via tunnelling of electrons between the two quantum dots(7-9). We coherently control the qubits using electrically driven spin resonance(10,11) in isotopically enriched silicon(12 28)Si, attaining single-qubit gate fidelities of 98.6 per cent and a coherence time of 2 microseconds during '  hot'  operation, comparable to those of spin qubits in natural silicon at millikelvin temperatures(13-16). Furthermore, we show that the unit cell can be operated at magnetic fields as low as 0.1 tesla, corresponding to a qubit control frequency of 3.5 gigahertz, where the qubit energy is well below the thermal energy. The unit cell constitutes the core building block of a full-scale silicon quantum computer and satisfies layout constraints required by error-correction architectures(8),(17). Our work indicates that a spin-based quantum computer could be operated at increased temperatures in a simple pumped He-4 system (which provides cooling power orders of magnitude higher than that of dilution refrigerators), thus potentially enabling the integration of classical control electronics with the qubit array(18,19).


  
Spin-cooling of the motion of a trapped diamond 期刊论文
NATURE, 2020
作者:  Auer, Thomas O.;  Khallaf, Mohammed A.;  Silbering, Ana F.;  Zappia, Giovanna;  Ellis, Kaitlyn;  Alvarez-Ocana, Raquel;  Arguello, J. Roman;  Hansson, Bill S.;  Jefferis, Gregory S. X. E.;  Caron, Sophie J. C.;  Knaden, Markus;  Benton, Richard
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Coupling the spins of many nitrogen-vacancy centres in a trapped diamond to its orientation produces a spin-dependent torque and spin-cooling of the motion of the diamond.


Observing and controlling macroscopic quantum systems has long been a driving force in quantum physics research. In particular, strong coupling between individual quantum systems and mechanical oscillators is being actively studied(1-3). Whereas both read-out of mechanical motion using coherent control of spin systems(4-9) and single-spin read-out using pristine oscillators have been demonstrated(10,11), temperature control of the motion of a macroscopic object using long-lived electronic spins has not been reported. Here we observe a spin-dependent torque and spin-cooling of the motion of a trapped microdiamond. Using a combination of microwave and laser excitation enables the spins of nitrogen-vacancy centres to act on the diamond orientation and to cool the diamond libration via a dynamical back-action. Furthermore, by driving the system in the nonlinear regime, we demonstrate bistability and self-sustained coherent oscillations stimulated by spin-mechanical coupling, which offers the prospect of spin-driven generation of non-classical states of motion. Such a levitating diamond-held in position by electric field gradients under vacuum-can operate as a '  compass'  with controlled dissipation and has potential use in high-precision torque sensing(12-14), emulation of the spin-boson problem(15) and probing of quantum phase transitions(16). In the single-spin limit(17) and using ultrapure nanoscale diamonds, it could allow quantum non-demolition read-out of the spin of nitrogen-vacancy centres at ambient conditions, deterministic entanglement between distant individual spins(18) and matter-wave interferometry(16,19,20).


  
An intestinal zinc sensor regulates food intake and developmental growth 期刊论文
NATURE, 2020, 580 (7802) : 263-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.


In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment(1). In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system  however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes(1). Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.


  
gamma delta T cells and adipocyte IL-17RC control fat innervation and thermogenesis 期刊论文
NATURE, 2020, 578 (7796) : 610-+
作者:  Staus, Dean P.;  Hu, Hongli;  Robertson, Michael J.;  Kleinhenz, Alissa L. W.;  Wingler, Laura M.;  Capel, William D.;  Latorraca, Naomi R.;  Lefkowitz, Robert J.;  Skiniotis, Georgios
收藏  |  浏览/下载:50/0  |  提交时间:2020/07/03

V gamma 6(+) V delta 1(+) gamma delta T cells control tolerance to cold by activating adipocyte IL-17RC and promoting sympathetic innervation of thermogenic adipose tissue in mice.


The sympathetic nervous system innervates peripheral organs to regulate their function and maintain homeostasis, whereas target cells also produce neurotrophic factors to promote sympathetic innervation(1,2). The molecular basis of this bi-directional communication remains to be fully determined. Here we use thermogenic adipose tissue from mice as a model system to show that T cells, specifically gamma delta T cells, have a crucial role in promoting sympathetic innervation, at least in part by driving the expression of TGF beta 1 in parenchymal cells via the IL-17 receptor C (IL-17RC). Ablation of IL-17RC specifically in adipose tissue reduces expression of TGF beta 1 in adipocytes, impairs local sympathetic innervation and causes obesity and other metabolic phenotypes that are consistent with defective thermogenesis  innervation can be fully rescued by restoring TGF beta 1 expression. Ablating gamma delta tau cells and the IL-17RC signalling pathway also impairs sympathetic innervation in other tissues such as salivary glands. These findings demonstrate coordination between T cells and parenchymal cells to regulate sympathetic innervation.


  
Ice front blocking of ocean heat transport to an Antarctic ice shelf 期刊论文
NATURE, 2020, 578 (7796) : 568-+
作者:  Alexandrov, Ludmil B.;  Kim, Jaegil;  Haradhvala, Nicholas J.;  Huang, Mi Ni;  Ng, Alvin Wei Tian;  Wu, Yang;  Boot, Arnoud;  Covington, Kyle R.;  Gordenin, Dmitry A.;  Bergstrom, Erik N.;  Islam, S. M. Ashiqul;  Lopez-Bigas, Nuria;  Klimczak, Leszek J.;  McPherson, John R.;  Morganella, Sandro;  Sabarinathan, Radhakrishnan;  Wheeler, David A.;  Mustonen, Ville;  Getz, Gad;  Rozen, Steven G.;  Stratton, Michael R.
收藏  |  浏览/下载:12/0  |  提交时间:2020/05/13

The front of the Getz Ice Shelf in West Antarctica creates an abrupt topographic step that deflects ocean currents, suppressing 70% of the heat delivery to the ice sheet.


Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate(1,2). Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change(2,3), motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice(4-6). However, the shoreward heat flux typically far exceeds that required to match observed melt rates(2,7,8), suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf(9). Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.