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Impaired cell fate through gain-of-function mutations in a chromatin reader 期刊论文
NATURE, 2020, 577 (7788) : 121-+
作者:  Wan, Liling;  Chong, Shasha;  Xuan, Fan;  Liang, Angela;  Cui, Xiaodong;  Gates, Leah;  Carroll, Thomas S.;  Li, Yuanyuan;  Feng, Lijuan;  Chen, Guochao;  Wang, Shu-Ping;  Ortiz, Michael V.;  Daley, Sara K.;  Wang, Xiaolu;  Xuan, Hongwen;  Kentsis, Alex;  Muir, Tom W.;  Roeder, Robert G.;  Li, Haitao;  Li, Wei;  Tjian, Robert;  Wen, Hong;  Allis, C. David
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by '  reader'  proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatinreader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.


  
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:20/0  |  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.


  
Intensive farming drives long-term shifts in avian community composition 期刊论文
NATURE, 2020, 579 (7799) : 393-+
作者:  Oh, Eugene;  Mark, Kevin G.;  Mocciaro, Annamaria;  Watson, Edmond R.;  Prabu, J. Rajan;  Cha, Denny D.;  Kampmann, Martin;  Gamarra, Nathan;  Zhou, Coral Y.;  Rape, Michael
收藏  |  浏览/下载:28/0  |  提交时间:2020/05/13

Variation in vegetation and climate affects the long-term changes in bird communities in intensive-agriculture habitats, but not in diversified-agriculture or natural-forest habitats, by changing the local colonization and extinction rates.


Agricultural practices constitute both the greatest cause of biodiversity loss and the greatest opportunity for conservation(1,2), given the shrinking scope of protected areas in many regions. Recent studies have documented the high levels of biodiversity-across many taxa and biomes-that agricultural landscapes can support over the short term(1,3,4). However, little is known about the long-term effects of alternative agricultural practices on ecological communities(4,5) Here we document changes in bird communities in intensive-agriculture, diversified-agriculture and natural-forest habitats in 4 regions of Costa Rica over a period of 18 years. Long-term directional shifts in bird communities were evident in intensive- and diversified-agricultural habitats, but were strongest in intensive-agricultural habitats, where the number of endemic and International Union for Conservation of Nature (IUCN) Red List species fell over time. All major guilds, including those involved in pest control, pollination and seed dispersal, were affected. Bird communities in intensive-agricultural habitats proved more susceptible to changes in climate, with hotter and drier periods associated with greater changes in community composition in these settings. These findings demonstrate that diversified agriculture can help to alleviate the long-term loss of biodiversity outside natural protected areas(1).


  
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:77/0  |  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.


  
Spontaneous gyrotropic electronic order in a transition-metal dichalcogenide 期刊论文
NATURE, 2020, 578 (7796) : 545-+
作者:  Kum, Hyun S.;  Lee, Hyungwoo;  Kim, Sungkyu;  Lindemann, Shane;  Kong, Wei;  Qiao, Kuan;  Chen, Peng;  Irwin, Julian;  Lee, June Hyuk;  Xie, Saien;  Subramanian, Shruti;  Shim, Jaewoo;  Bae, Sang-Hoon;  Choi, Chanyeol;  Ranno, Luigi;  Seo, Seungju;  Lee, Sangho;  Bauer, Jackson;  Li, Huashan;  Lee, Kyusang;  Robinson, Joshua A.;  Ross, Caroline A.;  Schlom, Darrell G.;  Rzchowski, Mark S.;  Eom, Chang-Beom;  Kim, Jeehwan
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Chirality is ubiquitous in nature, and populations of opposite chiralities are surprisingly asymmetric at fundamental levels(1,2). Examples range from parity violation in the subatomic weak force to homochirality in biomolecules. The ability to achieve chirality-selective synthesis (chiral induction) is of great importance in stereochemistry, molecular biology and pharmacology(2). In condensed matter physics, a crystalline electronic system is geometrically chiral when it lacks mirror planes, space-inversion centres or rotoinversion axes(1). Typically, geometrical chirality is predefined by the chiral lattice structure of a material, which is fixed on formation of the crystal. By contrast, in materials with gyrotropic order(3-6), electrons spontaneously organize themselves to exhibit macroscopic chirality in an originally achiral lattice. Although such order-which has been proposed as the quantum analogue of cholesteric liquid crystals-has attracted considerable interest(3-15), no clear observation or manipulation of gyrotropic order has been achieved so far. Here we report the realization of optical chiral induction and the observation of a gyrotropically ordered phase in the transition-metal dichalcogenide semimetal 1T-TiSe2. We show that shining mid-infrared circularly polarized light on 1T-TiSe2 while cooling it below the critical temperature leads to the preferential formation of one chiral domain. The chirality of this state is confirmed by the measurement of an out-of-plane circular photogalvanic current, the direction of which depends on the optical induction. Although the role of domain walls requires further investigation with local probes, the methodology demonstrated here can be applied to realize and control chiral electronic phases in other quantum materials(4,16).


Optical chiral induction and spontaneous gyrotropic electronic order are realized in the transition-metal chalcogenide 1T-TiSe2 by using illumination with mid-infrared circularly polarized light and simultaneous cooling below the critical temperature.


  
Hidden diversity of vacancy networks in Prussian blue analogues 期刊论文
NATURE, 2020, 578 (7794) : 256-+
作者:  Hendrickx, N. W.;  Franke, D. P.;  Sammak, A.;  Scappucci, G.;  Veldhorst, M.
收藏  |  浏览/下载:30/0  |  提交时间:2020/07/03

Prussian blue analogues (PBAs) are a diverse family of microporous inorganic solids, known for their gas storage ability(1), metal-ion immobilization(2), proton conduction(3), and stimuli-dependent magnetic(4,5), electronic(6) and optical(7) properties. This family of materials includes the double-metal cyanide catalysts(8,9) and the hexacyanoferrate/ hexacyanomanganate battery materials(10,11). Central to the various physical properties of PBAs is their ability to reversibly transport mass, a process enabled by structural vacancies. Conventionally presumed to be random(12,13), vacancy arrangements are crucial because they control micropore-network characteristics, and hence the diffusivity and adsorption profiles(14,15). The long-standing obstacle to characterizing the vacancy networks of PBAs is the inaccessibility of single crystals(16). Here we report the growth of single crystals of various PBAs and the measurement and interpretation of their X-ray diffuse scattering patterns. We identify a diversity of non-random vacancy arrangements that is hidden from conventional crystallographic powder analysis. Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry. The hidden phase boundaries that emerge demarcate vacancynetwork polymorphs with very different micropore characteristics. Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiency.


  
Fast two-qubit logic with holes in germanium 期刊论文
NATURE, 2020, 577 (7791) : 487-+
作者:  Halpin-Healy, Tyler S.;  Klompe, Sanne E.;  Sternberg, Samuel H.;  Fernandez, Israel S.
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

Universal quantum information processing requires the execution of single-qubit and two-qubit logic. Across all qubit realizations(1), spin qubits in quantum dots have great promise to become the central building block for quantum computation(2). Excellent quantum dot control can be achieved in gallium arsenide(3-5), and high-fidelity qubit rotations and two-qubit logic have been demonstrated in silicon(6-9), but universal quantum logic implemented with local control has yet to be demonstrated. Here we make this step by combining all of these desirable aspects using hole quantum dots in germanium. Good control over tunnel coupling and detuning is obtained by exploiting quantum wells with very low disorder, enabling operation at the charge symmetry point for increased qubit performance. Spin-orbit coupling obviates the need for microscopic elements close to each qubit and enables rapid qubit control with driving frequencies exceeding 100 MHz. We demonstrate a fast universal quantum gate set composed of single-qubit gates with a fidelity of 99.3 per cent and a gate time of 20 nanoseconds, and two-qubit logic operations executed within 75 nanoseconds. Planar germanium has thus matured within a year from a material that can host quantum dots to a platform enabling two-qubit logic, positioning itself as an excellent material for use in quantum information applications.


Spin qubits based on hole states in strained germanium could offer the most scalable platform for quantum computation.


  
Economic, environmental and health co-benefits of the use of advanced control strategies for lighting in buildings of Mexico 期刊论文
ENERGY POLICY, 2018, 113: 401-409
作者:  Diaz-Mendez, S. E.;  Torres-Rodriguez, A. A.;  Abatal, M.;  Escalante Soberanis, M. A.;  Bassam, A.;  Pedraza-Basulto, G. K.
收藏  |  浏览/下载:26/0  |  提交时间:2019/04/09
Environmental and health concerns  Emission Factors and Intake factors  Air pollution  Local and global climate change  Energy saving  Control devices for lighting systems  
Emergent patterns and processes in urban hydrocarbon governance 期刊论文
ENERGY POLICY, 2017, 111
作者:  Fry, Matthew;  Brannstrom, Christian
收藏  |  浏览/下载:14/0  |  提交时间:2019/04/09
Corporate social responsibility  Hydraulic fracturing  Local control  Policy mobilities  Setback distance  Unconventional hydrocarbons