GSTDTAP

浏览/检索结果: 共42条,第1-10条 帮助

已选(0)清除 条数/页:   排序方式:
Deciphering human macrophage development at single-cell resolution 期刊论文
NATURE, 2020
作者:  Oberst, Polina;  Fievre, Sabine;  Baumann, Natalia;  Concetti, Cristina;  Bartolini, Giorgia;  Jabaudon, Denis
收藏  |  浏览/下载:20/0  |  提交时间:2020/07/03

Macrophages are the first cells of the nascent immune system to emerge during embryonic development. In mice, embryonic macrophages infiltrate developing organs, where they differentiate symbiotically into tissue-resident macrophages (TRMs)(1). However, our understanding of the origins and specialization of macrophages in human embryos is limited. Here we isolated CD45(+) haematopoietic cells from human embryos at Carnegie stages 11 to 23 and subjected them to transcriptomic profiling by single-cell RNA sequencing, followed by functional characterization of a population of CD45(+)CD34(+)CD44(+) yolk sac-derived myeloid-biased progenitors (YSMPs) by single-cell culture. We also mapped macrophage heterogeneity across multiple anatomical sites and identified diverse subsets, including various types of embryonic TRM (in the head, liver, lung and skin). We further traced the specification trajectories of TRMs from either yolk sac-derived primitive macrophages or YSMP-derived embryonic liver monocytes using both transcriptomic and developmental staging information, with a focus on microglia. Finally, we evaluated the molecular similarities between embryonic TRMs and their adult counterparts. Our data represent a comprehensive characterization of the spatiotemporal dynamics of early macrophage development during human embryogenesis, providing a reference for future studies of the development and function of human TRMs.


Single-cell RNA sequencing of haematopoietic cells from human embryos at different developmental stages sheds light on the development and specification of macrophages in different tissues.


  
The online competition between pro- and anti-vaccination views 期刊论文
NATURE, 2020, 582 (7811) : 230-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.


Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).


  
Fundamental bounds on the fidelity of sensory cortical coding 期刊论文
NATURE, 2020
作者:  Rempel, S.;  Gati, C.;  Nijland, M.;  Thangaratnarajah, C.;  Karyolaimos, A.;  de Gier, J. W.;  Guskov, A.;  Slotboom, D. J.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

How the brain processes information accurately despite stochastic neural activity is a longstanding question(1). For instance, perception is fundamentally limited by the information that the brain can extract from the noisy dynamics of sensory neurons. Seminal experiments(2,3) suggest that correlated noise in sensory cortical neural ensembles is what limits their coding accuracy(4-6), although how correlated noise affects neural codes remains debated(7-11). Recent theoretical work proposes that how a neural ensemble'  s sensory tuning properties relate statistically to its correlated noise patterns is a greater determinant of coding accuracy than is absolute noise strength(12-14). However, without simultaneous recordings from thousands of cortical neurons with shared sensory inputs, it is unknown whether correlated noise limits coding fidelity. Here we present a 16-beam, two-photon microscope to monitor activity across the mouse primary visual cortex, along with analyses to quantify the information conveyed by large neural ensembles. We found that, in the visual cortex, correlated noise constrained signalling for ensembles with 800-1,300 neurons. Several noise components of the ensemble dynamics grew proportionally to the ensemble size and the encoded visual signals, revealing the predicted information-limiting correlations(12-14). Notably, visual signals were perpendicular to the largest noise mode, which therefore did not limit coding fidelity. The information-limiting noise modes were approximately ten times smaller and concordant with mouse visual acuity(15). Therefore, cortical design principles appear to enhance coding accuracy by restricting around 90% of noise fluctuations to modes that do not limit signalling fidelity, whereas much weaker correlated noise modes inherently bound sensory discrimination.


A microscopy system that enables simultaneous recording from hundreds of neurons in the mouse visual cortex reveals that the brain enhances its coding capacity by representing visual inputs in dimensions perpendicular to correlated noise.


  
Simulation of Hubbard model physics in WSe2/WS2 moire superlattices 期刊论文
NATURE, 2020, 579 (7799) : 353-+
作者:  Stein, Reed M.;  Kang, Hye Jin;  McCorvy, John D.;  Glatfelter, Grant C.;  Jones, Anthony J.;  Che, Tao;  Slocum, Samuel;  Huang, Xi-Ping;  Savych, Olena;  Moroz, Yurii S.;  Stauch, Benjamin;  Johansson, Linda C.;  Cherezov, Vadim;  Kenakin, Terry;  Irwin, John J.;  Shoichet, Brian K.;  Roth, Bryan L.;  Dubocovich, Margarita L.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Study of WSe2/WS2 moire superlattices reveals the phase diagram of the triangular-lattice Hubbard model, including a Mott insulating state at half-filling and a possible magnetic quantum phase transition near 0.6 filling.


The Hubbard model, formulated by physicist John Hubbard in the 1960s(1), is a simple theoretical model of interacting quantum particles in a lattice. The model is thought to capture the essential physics of high-temperature superconductors, magnetic insulators and other complex quantum many-body ground states(2,3). Although the Hubbard model provides a greatly simplified representation of most real materials, it is nevertheless difficult to solve accurately except in the one-dimensional case(2,3). Therefore, the physical realization of the Hubbard model in two or three dimensions, which can act as an analogue quantum simulator (that is, it can mimic the model and simulate its phase diagram and dynamics(4,5)), has a vital role in solving the strong-correlation puzzle, namely, revealing the physics of a large number of strongly interacting quantum particles. Here we obtain the phase diagram of the two-dimensional triangular-lattice Hubbard model by studying angle-aligned WSe2/WS2 bilayers, which form moire superlattices(6) because of the difference between the lattice constants of the two materials. We probe the charge and magnetic properties of the system by measuring the dependence of its optical response on an out-of-plane magnetic field and on the gate-tuned carrier density. At half-filling of the first hole moire superlattice band, we observe a Mott insulating state with antiferromagnetic Curie-Weiss behaviour, as expected for a Hubbard model in the strong-interaction regime(2,3,7-9). Above half-filling, our experiment suggests a possible quantum phase transition from an antiferromagnetic to a weak ferromagnetic state at filling factors near 0.6. Our results establish a new solid-state platform based on moire superlattices that can be used to simulate problems in strong-correlation physics that are described by triangular-lattice Hubbard models.


  
Loopy Levy flights enhance tracer diffusion in active suspensions 期刊论文
NATURE, 2020, 579 (7799) : 364-+
作者:  Hu, Bo;  Jin, Chengcheng;  Zeng, Xing;  Resch, Jon M.;  Jedrychowski, Mark P.;  Yang, Zongfang;  Desai, Bhavna N.;  Banks, Alexander S.;  Lowell, Bradford B.;  Mathis, Diane;  Spiegelman, Bruce M.
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

A theoretical framework describing the hydrodynamic interactions between a passive particle and an active medium in out-of-equilibrium systems predicts long-range Levy flights for the diffusing particle driven by the density of the active component.


Brownian motion is widely used as a model of diffusion in equilibrium media throughout the physical, chemical and biological sciences. However, many real-world systems are intrinsically out of equilibrium owing to energy-dissipating active processes underlying their mechanical and dynamical features(1). The diffusion process followed by a passive tracer in prototypical active media, such as suspensions of active colloids or swimming microorganisms(2), differs considerably from Brownian motion, as revealed by a greatly enhanced diffusion coefficient(3-10) and non-Gaussian statistics of the tracer displacements(6,9,10). Although these characteristic features have been extensively observed experimentally, there is so far no comprehensive theory explaining how they emerge from the microscopic dynamics of the system. Here we develop a theoretical framework to model the hydrodynamic interactions between the tracer and the active swimmers, which shows that the tracer follows a non-Markovian coloured Poisson process that accounts for all empirical observations. The theory predicts a long-lived Levy flight regime(11) of the loopy tracer motion with a non-monotonic crossover between two different power-law exponents. The duration of this regime can be tuned by the swimmer density, suggesting that the optimal foraging strategy of swimming microorganisms might depend crucially on their density in order to exploit the Levy flights of nutrients(12). Our framework can be applied to address important theoretical questions, such as the thermodynamics of active systems(13), and practical ones, such as the interaction of swimming microorganisms with nutrients and other small particles(14) (for example, degraded plastic) and the design of artificial nanoscale machines(15).


  
Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids 期刊论文
NATURE, 2020
作者:  Nixon, Christopher C.;  Mavigner, Maud;  Sampey, Gavin C.;  Brooks, Alyssa D.;  Spagnuolo, Rae Ann;  Irlbeck, David M.;  Mattingly, Cameron;  Ho, Phong T.;  Schoof, Nils;  Cammon, Corinne G.;  Tharp, Greg K.;  Kanke, Matthew;  Wang, Zhang;  Cleary, Rachel A.;  Upadhyay, Amit A.;  De, Chandrav;  Wills, Saintedym R.;  Falcinelli, Shane D.;  Galardi, Cristin;  Walum, Hasse;  Schramm, Nathaniel J.;  Deutsch, Jennifer;  Lifson, Jeffrey D.;  Fennessey, Christine M.;  Keele, Brandon F.;  Jean, Sherrie;  Maguire, Sean;  Liao, Baolin;  Browne, Edward P.;  Ferris, Robert G.;  Brehm, Jessica H.;  Favre, David;  Vanderford, Thomas H.;  Bosinger, Steven E.;  Jones, Corbin D.;  Routy, Jean-Pierre;  Archin, Nancie M.;  Margolis, David M.;  Wahl, Angela;  Dunham, Richard M.;  Silvestri, Guido;  Chahroudi, Ann;  Garcia, J. Victor
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

Single-cell RNA sequencing and spatial transcriptomics reveal that the somitogenesis clock is active in mouse gastruloids, which can be induced to generate somites with the correct rostral-caudal patterning.


Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization(1-3). To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral-caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.


  
Classification with a disordered dopantatom network in silicon 期刊论文
NATURE, 2020, 577 (7790) : 341-+
作者:  Vagnozzi, Ronald J.;  Maillet, Marjorie;  Sargent, Michelle A.;  Khalil, Hadi;  Johansen, Anne Katrine Z.;  Schwanekamp, Jennifer A.;  York, Allen J.;  Huang, Vincent;  Nahrendorf, Matthias;  Sadayappan, Sakthivel;  Molkentin, Jeffery D.
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

Classification is an important task at which both biological and artificial neural networks excel(1,2). In machine learning, nonlinear projection into a high-dimensional feature space can make data linearly separable(3,4), simplifying the classification of complex features. Such nonlinear projections are computationally expensive in conventional computers. A promising approach is to exploit physical materials systems that perform this nonlinear projection intrinsically, because of their high computational density(5), inherent parallelism and energy efficiency(6,7). However, existing approaches either rely on the systems'  time dynamics, which requires sequential data processing and therefore hinders parallel computation(5,6,8), or employ large materials systems that are difficult to scale up(7). Here we use a parallel, nanoscale approach inspired by filters in the brain(1) and artificial neural networks(2) to perform nonlinear classification and feature extraction. We exploit the nonlinearity of hopping conduction(9-11) through an electrically tunable network of boron dopant atoms in silicon, reconfiguring the network through artificial evolution to realize different computational functions. We first solve the canonical two-input binary classification problem, realizing all Boolean logic gates(12) up to room temperature, demonstrating nonlinear classification with the nanomaterial system. We then evolve our dopant network to realize feature filters(2) that can perform four-input binary classification on the Modified National Institute of Standards and Technology handwritten digit database. Implementation of our material-based filters substantially improves the classification accuracy over that of a linear classifier directly applied to the original data(13). Our results establish a paradigm of silicon-based electronics for smallfootprint and energy-efficient computation(14).


  
Caveolae in CNS arterioles mediate neurovascular coupling 期刊论文
NATURE, 2020
作者:  Huang, Weijiao;  Masureel, Matthieu;  Qu, Qianhui;  Janetzko, John;  Inoue, Asuka;  Kato, Hideaki E.;  Robertson, Michael J.;  Nguyen, Khanh C.;  Glenn, Jeffrey S.;  Skiniotis, Georgios;  Kobilka, Brian K.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Caveolae in arteriolar endothelial cells-but not those in neighbouring smooth muscle cells-have a key role in neurovascular coupling, an essential function for meeting acute brain energy demand.


Proper brain function depends on neurovascular coupling: neural activity rapidly increases local blood flow to meet moment-to-moment changes in regional brain energy demand(1). Neurovascular coupling is the basis for functional brain imaging(2), and impaired neurovascular coupling is implicated in neurodegeneration(1). The underlying molecular and cellular mechanisms of neurovascular coupling remain poorly understood. The conventional view is that neurons or astrocytes release vasodilatory factors that act directly on smooth muscle cells (SMCs) to induce arterial dilation and increase local blood flow(1). Here, using two-photon microscopy to image neural activity and vascular dynamics simultaneously in the barrel cortex of awake mice under whisker stimulation, we found that arteriolar endothelial cells (aECs) have an active role in mediating neurovascular coupling. We found that aECs, unlike other vascular segments of endothelial cells in the central nervous system, have abundant caveolae. Acute genetic perturbations that eliminated caveolae in aECs, but not in neighbouring SMCs, impaired neurovascular coupling. Notably, caveolae function in aECs is independent of the endothelial NO synthase (eNOS)-mediated NO pathway. Ablation of both caveolae and eNOS completely abolished neurovascular coupling, whereas the single mutants exhibited partial impairment, revealing that the caveolae-mediated pathway in aECs is a major contributor to neurovascular coupling. Our findings indicate that vasodilation is largely mediated by endothelial cells that actively relay signals from the central nervous system to SMCs via a caveolae-dependent pathway.


  
Signatures of self-organized criticality in an ultracold atomic gas 期刊论文
NATURE, 2020, 577 (7791) : 481-+
作者:  MacPherson, Laura;  Anokye, Juliana;  Yeung, Miriam M.;  Lam, Enid Y. N.;  Chan, Yih-Chih;  Weng, Chen-Fang;  Yeh, Paul;  Knezevic, Kathy;  Butler, Miriam S.;  Hoegl, Annabelle;  Chan, Kah-Lok;  Burr, Marian L.;  Gearing, Linden J.;  Willson, Tracy;  Liu, Joy;  Choi, Jarny;  Yang, Yuqing;  Bilardi, Rebecca A.;  Falk, Hendrik;  Nghi Nguyen;  Stupple, Paul A.;  Peat, Thomas S.;  Zhang, Ming;  De Silva, Melanie;  Carrasco-Pozo, Catalina;  Avery, Vicky M.;  Khoo, Sim;  Dolezal, Olan;  Dennis, Matthew L.;  Nuttall, Stewart;  Surjadi, Regina;  Newman, Janet;  Ren, Bin;  Leaver, David J.;  Sun, Yuxin;  Baell, Jonathan B.;  Dovey, Oliver;  Vassiliou, George S.;  Grebien, Florian;  Dawson, Sarah-Jane;  Street, Ian P.;  Monahan, Brendon J.;  Burns, Christopher J.;  Choudhary, Chunaram;  Blewitt, Marnie E.;  Voss, Anne K.;  Thomas, Tim;  Dawson, Mark A.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Self-organized criticality is an elegant explanation of how complex structures emerge and persist throughout nature(1), and why such structures often exhibit similar scale-invariant properties(2-9). Although self-organized criticality is sometimes captured by simple models that feature a critical point as an attractor for the dynamics(10-15), the connection to real-world systems is exceptionally hard to test quantitatively(16-21). Here we observe three key signatures of self-organized criticality in the dynamics of a driven-dissipative gas of ultracold potassium atoms: self-organization to a stationary state that is largely independent of the initial conditions  scale-invariance of the final density characterized by a unique scaling function  and large fluctuations of the number of excited atoms (avalanches) obeying a characteristic power-law distribution. This work establishes a well-controlled platform for investigating self-organization phenomena and non-equilibrium criticality, with experimental access to the underlying microscopic details of the system.


A driven-dissipative gas of ultracold potassium atoms is used to demonstrate three key signatures of self-organized criticality, and provides a system in which the phenomenon can be experimentally tested.


  
Long-term cyclic persistence in an experimental predator-prey system 期刊论文
NATURE, 2020, 577 (7789) : 226-+
作者:  Blasius, Bernd;  Rudolf, Lars;  Weithoff, Guntram;  Gaedke, Ursula;  Fussmann, Gregor F.
收藏  |  浏览/下载:8/0  |  提交时间:2020/04/16

Predator-prey cycles rank among the most fundamental concepts in ecology, are predicted by the simplest ecological models and enable, theoretically, the indefinite persistence of predator and prey(1-4). However, it remains an open question for how long cyclic dynamics can be self-sustained in real communities. Field observations have been restricted to a few cycle periods(5-8) and experimental studies indicate that oscillations may be short-lived without external stabilizing factors(9-19). Here we performed microcosm experiments with a planktonic predator-prey system and repeatedly observed oscillatory time series of unprecedented length that persisted for up to around 50 cycles or approximately 300 predator generations. The dominant type of dynamics was characterized by regular, coherent oscillations with a nearly constant predator-prey phase difference. Despite constant experimental conditions, we also observed shorter episodes of irregular, non-coherent oscillations without any significant phase relationship. However, the predator-prey system showed a strong tendency to return to the dominant dynamical regime with a defined phase relationship. A mathematical model suggests that stochasticity is probably responsible for the reversible shift from coherent to non-coherent oscillations, a notion that was supported by experiments with external forcing by pulsed nutrient supply. Our findings empirically demonstrate the potential for infinite persistence of predator and prey populations in a cyclic dynamic regime that shows resilience in the presence of stochastic events.