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Synthesis and properties of free-standing monolayer amorphous carbon 期刊论文
NATURE, 2020, 577 (7789) : 199-+
作者:  Toh, Chee-Tat;  Zhang, Hongji;  Lin, Junhao;  Mayorov, Alexander S.;  Wang, Yun-Peng;  Orofeo, Carlo M.;  Ferry, Darim Badur;  Andersen, Henrik;  Kakenov, Nurbek;  Guo, Zenglong;  Abidi, Irfan Haider;  Sims, Hunter;  Suenaga, Kazu;  Pantelides, Sokrates T.;  Ozyilmaz, Barbaros
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

Bulk amorphous materials have been studied extensively and are widely used, yet their atomic arrangement remains an open issue. Although they are generally believed to be Zachariasen continuous random networks(1), recent experimental evidence favours the competing crystallite model in the case of amorphous silicon(2-4). In two-dimensional materials, however, the corresponding questions remain unanswered. Here we report the synthesis, by laser-assisted chemical vapour deposition(5), of centimetre-scale, free-standing, continuous and stable monolayer amorphous carbon, topologically distinct from disordered graphene. Unlike in bulk materials, the structure of monolayer amorphous carbon can be determined by atomic-resolution imaging. Extensive characterization by Raman and X-ray spectroscopy and transmission electron microscopy reveals the complete absence of long-range periodicity and a threefold-coordinated structure with a wide distribution of bond lengths, bond angles, and five-, six-, seven- and eight-member rings. The ring distribution is not a Zachariasen continuous random network, but resembles the competing (nano)crystallite model(6). We construct a corresponding model that enables density-functional-theory calculations of the properties of monolayer amorphous carbon, in accordance with observations. Direct measurements confirm that it is insulating, with resistivity values similar to those of boron nitride grown by chemical vapour deposition. Free-standing monolayer amorphous carbon is surprisingly stable and deforms to a high breaking strength, without crack propagation from the point of fracture. The excellent physical properties of this stable, free-standing monolayer amorphous carbon could prove useful for permeation and diffusion barriers in applications such as magnetic recording devices and flexible electronics.


  
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:17/0  |  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).


  
HBO1 is required for the maintenance of leukaemia stem cells 期刊论文
NATURE, 2020, 577 (7789) : 266-+
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, Poh 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:17/0  |  提交时间:2020/07/03

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)(1). Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HBO1 protein complex as critical regulators of LSC maintenance. Using CRISPR domain screening and quantitative mass spectrometry, we identified the histone acetyltransferase domain of HBO1 as being essential in the acetylation of histone H3 at K14. H3 acetylated at K14 (H3K14ac) facilitates the processivity of RNA polymerase II to maintain the high expression of key genes (including Hoxa9 and Hoxa10) that help to sustain the functional properties of LSCs. To leverage this dependency therapeutically, we developed a highly potent small-molecule inhibitor of HBO1 and demonstrate its mode of activity as a competitive analogue of acetyl-CoA. Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients. These biological, structural and chemical insights into a therapeutic target in AML will enable the clinical translation of these findings.


  
Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation throughS-palmitoylation (vol 573, pg 139, 2019) (Retraction of Vol 573, Pg 139, 2020) 期刊论文
NATURE, 2020, 583 (7814) : 154-154
作者:  Zhang, Hao;  Liu, Chun-Xiao;  Gazibegovic, Sasa;  Xu, Di;  Logan, John A.;  Wang, Guanzhong;  van Loo, Nick;  Bommer, Jouri D. S.;  de Moor, Michiel W. A.;  Car, Diana;  Op Het Veld, Roy L. M.;  van Veldhoven, Petrus J.;  Koelling, Sebastian;  Verheijen, Marcel A.;  Pendharkar, Mihir;  Pennachio, Daniel J.;  Shojaei, Borzoyeh;  Lee, Joon Sue;  Palmstrom, Chris J.;  Bakkers, Erik P. A. M.;  Sarma, S. Das;  Kouwenhoven, Leo P.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03
Origin of complexity in haemoglobin evolution 期刊论文
NATURE, 2020
作者:  Cheema, Suraj S.;  Kwon, Daewoong;  Shanker, Nirmaan;  dos Reis, Roberto;  Hsu, Shang-Lin;  Xiao, Jun;  Zhang, Haigang;  Wagner, Ryan;  Datar, Adhiraj;  McCarter, Margaret R.;  Serrao, Claudy R.;  Yadav, Ajay K.;  Karbasian, Golnaz;  Hsu, Cheng-Hsiang;  Tan, Ava J.;  Wang, Li-Chen;  Thakare, Vishal;  Zhang, Xiang;  Mehta, Apurva;  Karapetrova, Evguenia;  Chopdekar, Rajesh, V;  Shafer, Padraic;  Arenholz, Elke;  Hu, Chenming;  Proksch, Roger;  Ramesh, Ramamoorthy;  Ciston, Jim;  Salahuddin, Sayeef
收藏  |  浏览/下载:50/0  |  提交时间:2020/07/03

Most proteins associate into multimeric complexes with specific architectures(1,2), which often have functional properties such as cooperative ligand binding or allosteric regulation(3). No detailed knowledge is available about how any multimer and its functions arose during evolution. Here we use ancestral protein reconstruction and biophysical assays to elucidate the origins of vertebrate haemoglobin, a heterotetramer of paralogous alpha- and beta-subunits that mediates respiratory oxygen transport and exchange by cooperatively binding oxygen with moderate affinity. We show that modern haemoglobin evolved from an ancient monomer and characterize the historical '  missing link'  through which the modern tetramer evolved-a noncooperative homodimer with high oxygen affinity that existed before the gene duplication that generated distinct alpha- and beta-subunits. Reintroducing just two post-duplication historical substitutions into the ancestral protein is sufficient to cause strong tetramerization by creating favourable contacts with more ancient residues on the opposing subunit. These surface substitutions markedly reduce oxygen affinity and even confer cooperativity, because an ancient linkage between the oxygen binding site and the multimerization interface was already an intrinsic feature of the protein'  s structure. Our findings establish that evolution can produce new complex molecular structures and functions via simple genetic mechanisms that recruit existing biophysical features into higher-level architectures.


Experimental analysis of reconstructed ancestral globins reveals that haemoglobin'  s complex tetrameric structure and oxygen-binding functions evolved by simple genetic and biophysical mechanisms.


  
Olfactory receptor and circuit evolution promote host specialization 期刊论文
NATURE, 2020
作者:  Chen, Tse-An;  Chuu, Chih-Piao;  Tseng, Chien-Chih;  Wen, Chao-Kai;  Wong, H. -S. Philip;  Pan, Shuangyuan;  Li, Rongtan;  Chao, Tzu-Ang;  Chueh, Wei-Chen;  Zhang, Yanfeng;  Fu, Qiang;  Yakobson, Boris I.;  Chang, Wen-Hao;  Li, Lain-Jong
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

The evolution of animal behaviour is poorly understood(1,2). Despite numerous correlations between interspecific divergence in behaviour and nervous system structure and function, demonstrations of the genetic basis of these behavioural differences remain rare(3-5). Here we develop a neurogenetic model, Drosophila sechellia, a species that displays marked differences in behaviour compared to its close cousin Drosophila melanogaster(6,7), which are linked to its extreme specialization on noni fruit (Morinda citrifolia)(8-16). Using calcium imaging, we identify olfactory pathways in D. sechellia that detect volatiles emitted by the noni host. Our mutational analysis indicates roles for different olfactory receptors in long- and short-range attraction to noni, and our cross-species allele-transfer experiments demonstrate that the tuning of one of these receptors is important for species-specific host-seeking. We identify the molecular determinants of this functional change, and characterize their evolutionary origin and behavioural importance. We perform circuit tracing in the D. sechellia brain, and find that receptor adaptations are accompanied by increased sensory pooling onto interneurons as well as species-specific central projection patterns. This work reveals an accumulation of molecular, physiological and anatomical traits that are linked to behavioural divergence between species, and defines a model for investigating speciation and the evolution of the nervous system.


A neurogenetic model, Drosophila sechellia-a relative of Drosophila melanogaster that has developed an extreme specialization for a single host plant-sheds light on the evolution of interspecific differences in behaviour.


  
Premature mortality related to United States cross-state air pollution 期刊论文
NATURE, 2020, 578 (7794) : 261-+
作者:  Helmink, Beth A.;  Reddy, Sangeetha M.;  Gao, Jianjun;  Zhang, Shaojun;  Basar, Rafet;  Thakur, Rohit;  Yizhak, Keren;  Sade-Feldman, Moshe;  Blando, Jorge;  Han, Guangchun;  Gopalakrishnan, Vancheswaran;  Xi, Yuanxin;  Zhao, Hao;  Amaria, Rodabe N.;  Tawbi, Hussein A.;  Cogdill, Alex P.;  Liu, Wenbin;  LeBleu, Valerie S.;  Kugeratski, Fernanda G.;  Patel, Sapna;  Davies, Michael A.;  Hwu, Patrick;  Lee, Jeffrey E.;  Gershenwald, Jeffrey E.;  Lucci, Anthony;  Arora, Reetakshi;  Woodman, Scott;  Keung, Emily Z.;  Gaudreau, Pierre-Olivier;  Reuben, Alexandre;  Spencer, Christine N.;  Burton, Elizabeth M.;  Haydu, Lauren E.;  Lazar, Alexander J.;  Zapassodi, Roberta;  Hudgens, Courtney W.;  Ledesma, Deborah A.;  Ong, SuFey;  Bailey, Michael;  Warren, Sarah;  Rao, Disha;  Krijgsman, Oscar;  Rozeman, Elisa A.;  Peeper, Daniel;  Blank, Christian U.;  Schumacher, Ton N.;  Butterfield, Lisa H.;  Zelazowska, Monika A.;  McBride, Kevin M.;  Kalluri, Raghu;  Allison, James;  Petitprez, Florent;  Fridman, Wolf Herman;  Sautes-Fridman, Catherine;  Hacohen, Nir;  Rezvani, Katayoun;  Sharma, Padmanee;  Tetzlaff, Michael T.;  Wang, Linghua;  Wargo, Jennifer A.
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

Outdoor air pollution adversely affects human health and is estimated to be responsible for five to ten per cent of the total annual premature mortality in the contiguous United States(1-3). Combustion emissions from a variety of sources, such as power generation or road traffic, make a large contribution to harmful air pollutants such as ozone and fine particulate matter (PM2.5)(4). Efforts to mitigate air pollution have focused mainly on the relationship between local emission sources and local air quality(2). Air quality can also be affected by distant emission sources, however, including emissions from neighbouring federal states(5,6). This cross-state exchange of pollution poses additional regulatory challenges. Here we quantify the exchange of air pollution among the contiguous United States, and assess its impact on premature mortality that is linked to increased human exposure to PM2.5 and ozone from seven emission sectors for 2005 to 2018. On average, we find that 41 to 53 per cent of air-quality-related premature mortality resulting from a state'  s emissions occurs outside that state. We also find variations in the cross-state contributions of different emission sectors and chemical species to premature mortality, and changes in these variations over time. Emissions from electric power generation have the greatest cross-state impacts as a fraction of their total impacts, whereas commercial/residential emissions have the smallest. However, reductions in emissions from electric power generation since 2005 have meant that, by 2018, cross-state premature mortality associated with the commercial/residential sector was twice that associated with power generation. In terms of the chemical species emitted, nitrogen oxides and sulfur dioxide emissions caused the most cross-state premature deaths in 2005, but by 2018 primary PM2.5 emissions led to cross-state premature deaths equal to three times those associated with sulfur dioxide emissions. These reported shifts in emission sectors and emission species that contribute to premature mortality may help to guide improvements to air quality in the contiguous United States.


  
Modular and tunable biological feedback control using a de novo protein switch (vol 572, pg 265, 2019) 期刊论文
NATURE, 2020, 579 (7798) : E8-E8
作者:  Christodoulou, Constantina;  Spencer, Joel A.;  Yeh, Shu-Chi A.;  Turcotte, Raphael;  Kokkaliaris, Konstantinos D.;  Panero, Riccardo;  Ramos, Azucena;  Guo, Guoji;  Seyedhassantehrani, Negar;  Esipova, Tatiana V.;  Vinogradov, Sergei A.;  Rudzinskas, Sarah;  Zhang, Yi;  Perkins, Archibald S.;  Orkin, Stuart H.;  Calogero, Raffaele A.;  Schroeder, Timm;  Lin, Charles P.;  Camargo, Fernando D.
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03
Mechanical regulation of glycolysis via cytoskeleton architecture 期刊论文
NATURE, 2020, 578 (7796) : 621-+
作者:  Faivre, Emily J.;  McDaniel, Keith F.;  Albert, Daniel H.;  Mantena, Srinivasa R.;  Plotnik, Joshua P.;  Wilcox, Denise;  Zhang, Lu;  Bui, Mai H.;  Sheppard, George S.;  Wang, Le;  Sehgal, Vasudha;  Lin, Xiaoyu;  Huang, Xiaoli;  Lu, Xin;  Uziel, Tamar;  Hessler, Paul;  Lam, Lloyd T.;  Bellin, Richard J.;  Mehta, Gaurav;  Fidanze, Steve;  Pratt, John K.;  Liu, Dachun;  Hasvold, Lisa A.;  Sun, Chaohong;  Panchal, Sanjay C.;  Nicolette, John J.;  Fossey, Stacey L.;  Park, Chang H.;  Longenecker, Kenton;  Bigelow, Lance;  Torrent, Maricel;  Rosenberg, Saul H.;  Kati, Warren M.;  Shen, Yu
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

The mechanics of the cellular microenvironment continuously modulates cell functions such as growth, survival, apoptosis, differentiation and morphogenesis via cytoskeletal remodelling and actomyosin contractility(1-3). Although all of these processes consume energy(4,5), it is unknown whether and how cells adapt their metabolic activity to variable mechanical cues. Here we report that the transfer of human bronchial epithelial cells from stiff to soft substrates causes a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme phosphofructokinase (PFK). PFK degradation is triggered by the disassembly of stress fibres, which releases the PFK-targeting E3 ubiquitin ligase tripartite motif (TRIM)-containing protein 21 (TRIM21). Transformed non-small-cell lung cancer cells, which maintain high glycolytic rates regardless of changing environmental mechanics, retain PFK expression by downregulating TRIM21, and by sequestering residual TRIM21 on a stress-fibre subset that is insensitive to substrate stiffness. Our data reveal a mechanism by which glycolysis responds to architectural features of the actomyosin cytoskeleton, thus coupling cell metabolism to the mechanical properties of the surrounding tissue. These processes enable normal cells to tune energy production in variable microenvironments, whereas the resistance of the cytoskeleton in response to mechanical cues enables the persistence of high glycolytic rates in cancer cells despite constant alterations of the tumour tissue.


Glycolysis in normal epithelial cells responds to microenvironmental mechanics via the modulation of actin bundles that sequester the phosphofructokinase-targeting ubiquitin ligase TRIM21, a process superseded by persistent actin bundles in cancer cells.


  
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.