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Spectroscopic confirmation of a mature galaxy cluster at a redshift of 2 期刊论文
NATURE, 2020, 577 (7788) : 39-+
作者:  Willis, J. P.;  Canning, R. E. A.;  Noordeh, E. S.;  Allen, S. W.;  King, A. L.;  Mantz, A.;  Morris, R. G.;  Stanford, S. A.;  Brammer, G.
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Galaxy clusters are the most massive virialized structures in the Universe and are formed through the gravitational accretion of matter over cosmic time(1). The discovery(2) of an evolved galaxy cluster at redshift z = 2, corresponding to a look-back time of 10.4 billion years, provides an opportunity to study its properties. The galaxy cluster XLSSC 122 was originally detected as a faint, extended X-ray source in the XMM Large Scale Structure survey and was revealed to be coincident with a compact over-density of galaxies(2) with photometric redshifts of 1.9 +/- 0.2. Subsequent observations3 at millimetre wavelengths detected a Sunyaev-Zel'  dovich decrement along the line of sight to XLSSC 122, thus confirming the existence of hot intracluster gas, while deep imaging spectroscopy from the European Space Agency'  s X-ray Multi-Mirror Mission (XMM-Newton) revealed(4) an extended, X-ray-bright gaseous atmosphere with a virial temperature of 60 million Kelvin, enriched with metals to the same extent as are local clusters. Here we report optical spectroscopic observations of XLSSC 122 and identify 37 member galaxies at a mean redshift of 1.98, corresponding to a look-back time of 10.4 billion years. We use photometry to determine a mean, dust-free stellar age of 2.98 billion years, indicating that star formation commenced in these galaxies at a mean redshift of 12, when the Universe was only 370 million years old. The full range of inferred formation redshifts, including the effects of dust, covers the interval from 7 to 13. These observations confirm that XLSSC 122 is a remarkably mature galaxy cluster with both evolved stellar populations in the member galaxies and a hot, metal-rich gas composing the intracluster medium.


  
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.


  
Engineering covalently bonded 2D layered materials by self-intercalation 期刊论文
NATURE, 2020, 581 (7807) : 171-+
作者:  Shang, Jian;  Ye, Gang;  Shi, Ke;  Wan, Yushun;  Luo, Chuming;  Aihara, Hideki;  Geng, Qibin;  Auerbach, Ashley;  Li, Fang
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Two-dimensional (2D) materials(1-5) offer a unique platform from which to explore the physics of topology and many-body phenomena. New properties can be generated by filling the van der Waals gap of 2D materials with intercalants(6,7)  however, post-growth intercalation has usually been limited to alkali metals(8-10). Here we show that the self-intercalation of native atoms(11,12) into bilayer transition metal dichalcogenides during growth generates a class of ultrathin, covalently bonded materials, which we name ic-2D. The stoichiometry of these materials is defined by periodic occupancy patterns of the octahedral vacancy sites in the van der Waals gap, and their properties can be tuned by varying the coverage and the spatial arrangement of the filled sites(7,13). By performing growth under high metal chemical potential(14,15) we can access a range of tantalum-intercalated TaS(Se)(y), including 25% Ta-intercalated Ta9S16, 33.3% Ta-intercalated Ta7S12, 50% Ta-intercalated Ta10S16, 66.7% Ta-intercalated Ta8Se12 (which forms a Kagome lattice) and 100% Ta-intercalated Ta9Se12. Ferromagnetic order was detected in some of these intercalated phases. We also demonstrate that self-intercalated V11S16, In11Se16 and FexTey can be grown under metal-rich conditions. Our work establishes self-intercalation as an approach through which to grow a new class of 2D materials with stoichiometry- or composition-dependent properties.


  
The proteome landscape of the kingdoms of life 期刊论文
NATURE, 2020
作者:  Arzi, Anat;  Rozenkrantz, Liron;  Gorodisky, Lior;  Rozenkrantz, Danit;  Holtzman, Yael;  Ravia, Aharon;  Bekinschtein, Tristan A.;  Galperin, Tatyana;  Krimchansky, Ben-Zion;  Cohen, Gal;  Oksamitni, Anna;  Aidinoff, Elena;  Sacher, Yaron;  Sobel, Noam
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Proteins carry out the vast majority of functions in all biological domains, but for technological reasons their large-scale investigation has lagged behind the study of genomes. Since the first essentially complete eukaryotic proteome was reported(1), advances in mass-spectrometry-based proteomics(2)have enabled increasingly comprehensive identification and quantification of the human proteome(3-6). However, there have been few comparisons across species(7,8), in stark contrast with genomics initiatives(9). Here we use an advanced proteomics workflow-in which the peptide separation step is performed by a microstructured and extremely reproducible chromatographic system-for the in-depth study of 100 taxonomically diverse organisms. With two million peptide and 340,000 stringent protein identifications obtained in a standardized manner, we double the number of proteins with solid experimental evidence known to the scientific community. The data also provide a large-scale case study for sequence-based machine learning, as we demonstrate by experimentally confirming the predicted properties of peptides fromBacteroides uniformis. Our results offer a comparative view of the functional organization of organisms across the entire evolutionary range. A remarkably high fraction of the total proteome mass in all kingdoms is dedicated to protein homeostasis and folding, highlighting the biological challenge of maintaining protein structure in all branches of life. Likewise, a universally high fraction is involved in supplying energy resources, although these pathways range from photosynthesis through iron sulfur metabolism to carbohydrate metabolism. Generally, however, proteins and proteomes are remarkably diverse between organisms, and they can readily be explored and functionally compared at www.proteomesoflife.org.


  
Editorial Expression of Concern: Exploring the quantum speed limit with computer games 期刊论文
NATURE, 2020, 581 (7808) : E7-E7
作者:  Friedman, Joseph;  York, Hunter;  Graetz, Nicholas;  Woyczynski, Lauren;  Whisnant, Joanna;  Hay, Simon I.;  Gakidou, Emmanuela
收藏  |  浏览/下载:1/0  |  提交时间:2020/07/03
Very regular high-frequency pulsation modes in young intermediate-mass stars 期刊论文
NATURE, 2020, 581 (7807) : 147-+
作者:  Zhao, Chuangqi;  Zhang, Pengchao;  Zhou, Jiajia;  Qi, Shuanhu;  Yamauchi, Yoshihiro;  Shi, Ruirui;  Fang, Ruochen;  Ishida, Yasuhiro;  Wang, Shutao;  Tomsia, Antoni P.;  Jiang, Lei;  Liu, Mingjie
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Asteroseismology probes the internal structures of stars by using their natural pulsation frequencies(1). It relies on identifying sequences of pulsation modes that can be compared with theoretical models, which has been done successfully for many classes of pulsators, including low-mass solar-type stars(2), red giants(3), high-mass stars(4) and white dwarfs(5). However, a large group of pulsating stars of intermediate mass-the so-called delta Scuti stars-have rich pulsation spectra for which systematic mode identification has not hitherto been possible(6,7). This arises because only a seemingly random subset of possible modes are excited and because rapid rotation tends to spoil regular patterns(8-10). Here we report the detection of remarkably regular sequences of high-frequency pulsation modes in 60 intermediate-mass main-sequence stars, which enables definitive mode identification. The space motions of some of these stars indicate that they are members of known associations of young stars, as confirmed by modelling of their pulsation spectra.


The pulsation spectra of intermediate-mass stars (so-called delta Scuti stars) have been challenging to analyse, but new observations of 60 such stars reveal remarkably regular sequences of high-frequency pulsation modes.


  
The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes 期刊论文
NATURE, 2020
作者:  Kindem, Jonathan M.;  Ruskuc, Andrei;  Bartholomew, John G.;  Rochman, Jake;  Huan, Yan Qi;  Faraon, Andrei
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

Analysis of Icelandic genomes reveals chromosome fragments of Neanderthal and Denisovan origin, the latter of which occurred through Denisovan gene flow either into ancestors of the Neanderthals or directly into humans.


Human evolutionary history is rich with the interbreeding of divergent populations. Most humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50-60 thousand years ago(1). Here we examine the effect of this event using 14.4 million putative archaic chromosome fragments that were detected in fully phased whole-genome sequences from 27,566 Icelanders, corresponding to a range of 56,388-112,709 unique archaic fragments that cover 38.0-48.2% of the callable genome. On the basis of the similarity with known archaic genomes, we assign 84.5% of fragments to an Altai or Vindija Neanderthal origin and 3.3% to Denisovan origin  12.2% of fragments are of unknown origin. We find that Icelanders have more Denisovan-like fragments than expected through incomplete lineage sorting. This is best explained by Denisovan gene flow, either into ancestors of the introgressing Neanderthals or directly into humans. A within-individual, paired comparison of archaic fragments with syntenic non-archaic fragments revealed that, although the overall rate of mutation was similar in humans and Neanderthals during the 500 thousand years that their lineages were separate, there were differences in the relative frequencies of mutation types-perhaps due to different generation intervals for males and females. Finally, we assessed 271 phenotypes, report 5 associations driven by variants in archaic fragments and show that the majority of previously reported associations are better explained by non-archaic variants.


  
Spin squeezing of 10(11) atoms by prediction and retrodiction measurements 期刊论文
NATURE, 2020, 581 (7807) : 159-+
作者:  Lan, Jun;  Ge, Jiwan;  Yu, Jinfang;  Shan, Sisi;  Zhou, Huan;  Fan, Shilong;  Zhang, Qi;  Shi, Xuanling;  Wang, Qisheng;  Zhang, Linqi;  Wang, Xinquan
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

The measurement sensitivity of quantum probes using N uncorrelated particles is restricted by the standard quantum limit(1), which is proportional to 1/root N. This limit, however, can be overcome by exploiting quantum entangled states, such as spin-squeezed states(2). Here we report the measurement-based generation of a quantum state that exceeds the standard quantum limit for probing the collective spin of 10(11) rubidium atoms contained in a macroscopic vapour cell. The state is prepared and verified by sequences of stroboscopic quantum non-demolition (QND) measurements. We then apply the theory of past quantum states(3,4) to obtain spin state information from the outcomes of both earlier and later QND measurements. Rather than establishing a physically squeezed state in the laboratory, the past quantum state represents the combined system information from these prediction and retrodiction measurements. This information is equivalent to a noise reduction of 5.6 decibels and a metrologically relevant squeezing of 4.5 decibels relative to the coherent spin state. The past quantum state yields tighter constraints on the spin component than those obtained by conventional QND measurements. Our measurement uses 1,000 times more atoms than previous squeezing experiments(5-10), with a corresponding angular variance of the squeezed collective spin of 4.6 x 10(-13) radians squared. Although this work is rooted in the foundational theory of quantum measurements, it may find practical use in quantum metrology and quantum parameter estimation, as we demonstrate by applying our protocol to quantum enhanced atomic magnetometry.


  
The dental proteome of Homo antecessor 期刊论文
NATURE, 2020, 580 (7802) : 235-+
作者:  Abram, Nerilie J.;  Wright, Nicky M.;  Ellis, Bethany;  Dixon, Bronwyn C.;  Wurtzel, Jennifer B.;  England, Matthew H.;  Ummenhofer, Caroline C.;  Philibosian, Belle;  Cahyarini, Sri Yudawati;  Yu, Tsai-Luen;  Shen, Chuan-Chou;  Cheng, Hai;  Edwards, R. Lawrence;  Heslop, David
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.


The phylogenetic relationships between hominins of the Early Pleistocene epoch in Eurasia, such as Homo antecessor, and hominins that appear later in the fossil record during the Middle Pleistocene epoch, such as Homo sapiens, are highly debated(1-5). For the oldest remains, the molecular study of these relationships is hindered by the degradation of ancient DNA. However, recent research has demonstrated that the analysis of ancient proteins can address this challenge(6-8). Here we present the dental enamel proteomes of H. antecessor from Atapuerca (Spain)(9,10) and Homo erectus from Dmanisi (Georgia)(1), two key fossil assemblages that have a central role in models of Pleistocene hominin morphology, dispersal and divergence. We provide evidence that H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans. This placement implies that the modern-like face of H. antecessor-that is, similar to that of modern humans-may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form. By recovering AMELY-specific peptide sequences, we also conclude that the H. antecessor molar fragment from Atapuerca that we analysed belonged to a male individual. Finally, these H. antecessor and H. erectus fossils preserve evidence of enamel proteome phosphorylation and proteolytic digestion that occurred in vivo during tooth formation. Our results provide important insights into the evolutionary relationships between H. antecessor and other hominin groups, and pave the way for future studies using enamel proteomes to investigate hominin biology across the existence of the genus Homo.


  
Germline Elongator mutations in Sonic Hedgehog medulloblastoma 期刊论文
NATURE, 2020, 580 (7803) : 396-+
作者:  Helmrich, S.;  Arias, A.;  Lochead, G.;  Wintermantel, T. M.;  Buchhold, M.;  Diehl, S.;  Whitlock, S.
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.