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Monumental architecture at Aguada Fenix and the rise of Maya civilization 期刊论文
NATURE, 2020
作者:  Bedding, Timothy R.;  Murphy, Simon J.;  Hey, Daniel R.;  Huber, Daniel;  Li, Tanda;  Smalley, Barry;  Stello, Dennis;  White, Timothy R.;  Ball, Warrick H.;  Chaplin, William J.;  Colman, Isabel L.;  Fuller, Jim;  Gaidos, Eric;  Harbeck, Daniel R.;  Hermes, J. J.;  Holdsworth, Daniel L.;  Li, Gang;  Li, Yaguang;  Mann, Andrew W.;  Reese, Daniel R.;  Sekaran, Sanjay;  Yu, Jie;  Antoci, Victoria;  Bergmann, Christoph;  Brown, Timothy M.;  Howard, Andrew W.;  Ireland, Michael J.;  Isaacson, Howard;  Jenkins, Jon M.;  Kjeldsen, Hans;  McCully, Curtis;  Rabus, Markus;  Rains, Adam D.;  Ricker, George R.;  Tinney, Christopher G.;  Vanderspek, Roland K.
收藏  |  浏览/下载:62/0  |  提交时间:2020/07/03

Archaeologists have traditionally thought that the development of Maya civilization was gradual, assuming that small villages began to emerge during the Middle Preclassic period (1000-350 bc  dates are calibrated throughout) along with the use of ceramics and the adoption of sedentism(1). Recent finds of early ceremonial complexes are beginning to challenge this model. Here we describe an airborne lidar survey and excavations of the previously unknown site of Aguada Fenix (Tabasco, Mexico) with an artificial plateau, which measures 1,400 m in length and 10 to 15 m in height and has 9 causeways radiating out from it. We dated this construction to between 1000 and 800 bc using a Bayesian analysis of radiocarbon dates. To our knowledge, this is the oldest monumental construction ever found in the Maya area and the largest in the entire pre-Hispanic history of the region. Although the site exhibits some similarities to the earlier Olmec centre of San Lorenzo, the community of Aguada Fenix probably did not have marked social inequality comparable to that of San Lorenzo. Aguada Fenix and other ceremonial complexes of the same period suggest the importance of communal work in the initial development of Maya civilization.


Lidar survey of the Maya lowlands uncovers the monumental site of Aguada Fenix, which dates to around 1000-800 bc and points to the role of communal construction in the development of Maya civilization.


  
Accurate compound-specific C-14 dating of archaeological pottery vessels 期刊论文
NATURE, 2020, 580 (7804) : 506-+
作者:  Yin, Yafei;  Lu, J. Yuyang;  Zhang, Xuechun;  Shao, Wen;  Xu, Yanhui;  Li, Pan;  Hong, Yantao;  Cui, Li;  Shan, Ge;  Tian, Bin;  Zhang, Qiangfeng Cliff;  Shen, Xiaohua
收藏  |  浏览/下载:35/0  |  提交时间:2020/05/13

Pottery is one of the most commonly recovered artefacts from archaeological sites. Despite more than a century of relative dating based on typology and seriation(1), accurate dating of pottery using the radiocarbon dating method has proven extremely challenging owing to the limited survival of organic temper and unreliability of visible residues(2-4). Here we report a method to directly date archaeological pottery based on accelerator mass spectrometry analysis of C-14 in absorbed food residues using palmitic (C-16:0) and stearic (C-18:0) fatty acids purified by preparative gas chromatography(5-8). We present accurate compound-specific radiocarbon determinations of lipids extracted from pottery vessels, which were rigorously evaluated by comparison with dendrochronological dates(9,10) and inclusion in site and regional chronologies that contained previously determined radiocarbon dates on other materials(11-15). Notably, the compound-specific dates from each of the C-16:0 and C-18:0 fatty acids in pottery vessels provide an internal quality control of the results(6) and are entirely compatible with dates for other commonly dated materials. Accurate radiocarbon dating of pottery vessels can reveal: (1) the period of use of pottery  (2) the antiquity of organic residues, including when specific foodstuffs were exploited  (3) the chronology of sites in the absence of traditionally datable materials  and (4) direct verification of pottery typochronologies. Here we used the method to date the exploitation of dairy and carcass products in Neolithic vessels from Britain, Anatolia, central and western Europe, and Saharan Africa.


Using lipid residues absorbed in potsherds, the ages of pottery from various archaeological sites are determined and validated using sites for which the dates are well known from other methods.


  
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:80/0  |  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.


  
Late-stage oxidative C(sp(3))-H methylation 期刊论文
NATURE, 2020, 580 (7805) : 621-+
作者:  Fessler, Evelyn;  Eckl, Eva-Maria;  Schmitt, Sabine;  Mancilla, Igor Alves;  Meyer-Bender, Matthias F.;  Hanf, Monika;  Philippou-Massier, Julia;  Krebs, Stefan;  Zischka, Hans;  Jae, Lucas T.
收藏  |  浏览/下载:71/0  |  提交时间:2020/07/03

Frequently referred to as the '  magic methyl effect'  , the installation of methyl groups-especially adjacent (alpha) to heteroatoms-has been shown to dramatically increase the potency of biologically active molecules(1-3). However, existing methylation methods show limited scope and have not been demonstrated in complex settings(1). Here we report a regioselective and chemoselective oxidative C(sp(3))-H methylation method that is compatible with late-stage functionalization of drug scaffolds and natural products. This combines a highly site-selective and chemoselective C-H hydroxylation with a mild, functional-group-tolerant methylation. Using a small-molecule manganese catalyst, Mn(CF3PDP), at low loading (at a substrate/catalyst ratio of 200) affords targeted C-H hydroxylation on heterocyclic cores, while preserving electron-neutral and electron-rich aryls. Fluorine- or Lewis-acid-assisted formation of reactive iminium or oxonium intermediates enables the use of a mildly nucleophilic organoaluminium methylating reagent that preserves other electrophilic functionalities on the substrate. We show this late-stage C(sp(3))-H methylation on 41 substrates housing 16 different medicinally important cores that include electron-rich aryls, heterocycles, carbonyls and amines. Eighteen pharmacologically relevant molecules with competing sites-including drugs (for example, tedizolid) and natural products-are methylated site-selectively at the most electron rich, least sterically hindered position. We demonstrate the syntheses of two magic methyl substrates-an inverse agonist for the nuclear receptor RORc and an antagonist of the sphingosine-1-phosphate receptor-1-via late-stage methylation from the drug or its advanced precursor. We also show a remote methylation of the B-ring carbocycle of an abiraterone analogue. The ability to methylate such complex molecules at late stages will reduce synthetic effort and thereby expedite broader exploration of the magic methyl effect in pursuit of new small-molecule therapeutics and chemical probes.


A manganese-catalysed oxidative C(sp(3))-H methylation method allows a methyl group to be selectively installed into medicinally important heterocycles, providing a way to improve pharmaceuticals and better understand the '  magic methyl effect'  .


  
Mott and generalized Wigner crystal states in WSe2/WS2 moire superlattices 期刊论文
NATURE, 2020, 579 (7799) : 359-+
作者:  Yuan, Jie;  Chang, Si-Yuan;  Yin, Shi-Gang;  Liu, Zhi-Yang;  Cheng, Xiu;  Liu, Xi-Juan;  Jiang, Qiang;  Gao, Ge;  Lin, De-Ying;  Kang, Xin-Lei;  Ye, Shi-Wei;  Chen, Zheng;  Yin, Jiang-An;  Hao, Pei;  Jiang, Lubin;  Cai, Shi-Qing
收藏  |  浏览/下载:76/0  |  提交时间:2020/07/03

Strongly correlated insulating Mott and generalized Wigner phases are detected in WSe2/WS2 moire superlattices, and their electrical properties and excited spin states are studied using an optical technique.


Moire superlattices can be used to engineer strongly correlated electronic states in two-dimensional van der Waals heterostructures, as recently demonstrated in the correlated insulating and superconducting states observed in magic-angle twisted-bilayer graphene and ABC trilayer graphene/boron nitride moire superlattices(1-4). Transition metal dichalcogenide moire heterostructures provide another model system for the study of correlated quantum phenomena(5) because of their strong light-matter interactions and large spin-orbit coupling. However, experimental observation of correlated insulating states in this system is challenging with traditional transport techniques. Here we report the optical detection of strongly correlated phases in semiconducting WSe2/WS2 moire superlattices. We use a sensitive optical detection technique and reveal a Mott insulator state at one hole per superlattice site and surprising insulating phases at 1/3 and 2/3 filling of the superlattice, which we assign to generalized Wigner crystallization on the underlying lattice(6-11). Furthermore, the spin-valley optical selection rules(12-14) of transition metal dichalcogenide heterostructures allow us to optically create and investigate low-energy excited spin states in the Mott insulator. We measure a very long spin relaxation lifetime of many microseconds in the Mott insulating state, orders of magnitude longer than that of charge excitations. Our studies highlight the value of using moire superlattices beyond graphene to explore correlated physics.


  
Nagaoka ferromagnetism observed in a quantum dot plaquette 期刊论文
NATURE, 2020, 579 (7800) : 528-533
作者:  Yu, Yong;  Ma, Fei;  Luo, Xi-Yu;  Jing, Bo;  Sun, Peng-Fei;  Fang, Ren-Zhou;  Yang, Chao-Wei;  Liu, Hui;  Zheng, Ming-Yang;  Xie, Xiu-Ping;  Zhang, Wei-Jun;  You, Li-Xing;  Wang, Zhen;  Chen, Teng-Yun;  Zhang, Qiang;  Bao, Xiao-Hui;  Pan, Jian-Wei
收藏  |  浏览/下载:52/0  |  提交时间:2020/07/03

A quantum dot device designed to host four electrons is used to demonstrate Nagaoka ferromagnetism-a model of itinerant magnetism that has so far been limited to theoretical investigation.


Engineered, highly controllable quantum systems are promising simulators of emergent physics beyond the simulation capabilities of classical computers(1). An important problem in many-body physics is itinerant magnetism, which originates purely from long-range interactions of free electrons and whose existence in real systems has been debated for decades(2,3). Here we use a quantum simulator consisting of a four-electron-site square plaquette of quantum dots(4) to demonstrate Nagaoka ferromagnetism(5). This form of itinerant magnetism has been rigorously studied theoretically(6-9) but has remained unattainable in experiments. We load the plaquette with three electrons and demonstrate the predicted emergence of spontaneous ferromagnetic correlations through pairwise measurements of spin. We find that the ferromagnetic ground state is remarkably robust to engineered disorder in the on-site potentials and we can induce a transition to the low-spin state by changing the plaquette topology to an open chain. This demonstration of Nagaoka ferromagnetism highlights that quantum simulators can be used to study physical phenomena that have not yet been observed in any experimental system. The work also constitutes an important step towards large-scale quantum dot simulators of correlated electron systems.


  
HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation 期刊论文
NATURE, 2020, 579 (7800) : 598-+
作者:  Yao, Peng;  Wu, Huaqiang;  Gao, Bin;  Tang, Jianshi;  Zhang, Qingtian;  Zhang, Wenqiang;  Yang, J. Joshua;  Qian, He
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

Assembly of a catalytic centre formed by HPF1 bound to PARP1 or PARP2 is essential for protein ADP-ribosylation after DNA damage in human cells.


The anti-cancer drug target poly(ADP-ribose) polymerase 1 (PARP1) and its close homologue, PARP2, are early responders to DNA damage in human cells(1,2). After binding to genomic lesions, these enzymes use NAD(+) to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors(3,4). These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues(5-10). Here we report a co-structure of HPF1 bound to the catalytic domain of PARP2 that, in combination with NMR and biochemical data, reveals a composite active site formed by residues from HPF1 and PARP1 or PARP2 . The assembly of this catalytic centre is essential for the addition of ADP-ribose moieties after DNA damage in human cells. In response to DNA damage and occupancy of the NAD(+)-binding site, the interaction of HPF1 with PARP1 or PARP2 is enhanced by allosteric networks that operate within the PARP proteins, providing an additional level of regulation in the induction of the DNA damage response. As HPF1 forms a joint active site with PARP1 or PARP2, our data implicate HPF1 as an important determinant of the response to clinical PARP inhibitors.


  
An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity 期刊论文
NATURE, 2020, 577 (7791) : 572-+
作者:  Athukoralage, Januka S.;  McMahon, Stephen A.;  Zhang, Changyi;  Grueschow, Sabine;  Graham, Shirley;  Krupovic, Mart;  Whitaker, Rachel J.;  Gloster, Tracey M.;  White, Malcolm F.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

The CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA)(1,2) and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)(3-5). Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain(6), sculpting a powerful antiviral response(7-10) that can drive viruses to extinction(7,8). Cyclic nucleotides are increasingly implicated in host-pathogen interactions(11-13). Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA(4)). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA(4) specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA(4) signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.


Bacteria and archaea use cyclic oligoadenylate molecules as part of the CRISPR system for antiviral defence  here, a family of viral enzymes that rapidly degrades cyclic oligoadenylates is identified and biochemically and structurally described.


  
Palaeoclimate evidence of vulnerable permafrost during times of low sea ice 期刊论文
NATURE, 2020, 577 (7789) : 221-+
作者:  Vaks, A.;  Mason, A. J.;  Breitenbach, S. F. M.;  Kononov, A. M.;  Osinzev, A. V.;  Rosensaft, M.;  Borshevsky, A.;  Gutareva, O. S.;  Henderson, G. M.
收藏  |  浏览/下载:33/0  |  提交时间:2020/05/13

Climate change in the Arctic is occurring rapidly, and projections suggest the complete loss of summer sea ice by the middle of this century(1). The sensitivity of permanently frozen ground (permafrost) in the Northern Hemisphere to warming is less clear, and its long-term trends are harder to monitor than those of sea ice. Here we use palaeoclimate data to show that Siberian permafrost is robust to warming when Arctic sea ice is present, but vulnerable when it is absent. Uranium-lead chronology of carbonate deposits (speleothems) in a Siberian cave located at the southern edge of continuous permafrost reveals periods in which the overlying ground was not permanently frozen. The speleothem record starts 1.5 million years ago (Ma), a time when greater equator-to-pole heat transport led to a warmer Northern Hemisphere(2). The growth of the speleothems indicates that permafrost at the cave site was absent at that time, becoming more frequent from about 1.35 Ma, as the Northern Hemisphere cooled, and permanent after about 0.4 Ma. This history mirrors that of year-round sea ice in the Arctic Ocean, which was largely absent before about 0.4 Ma (ref.(3)), but continuously present since that date. The robustness of permafrost when sea ice is present, as well as the increased permafrost vulnerability when sea ice is absent, can be explained by changes in both heat and moisture transport. Reduced sea ice may contribute to warming of Arctic air(4-6), which can lead to warming far inland(7). Open Arctic waters also increase the source of moisture and increase autumn snowfall over Siberia, insulating the ground from low winter temperatures(8-10). These processes explain the relationship between an ice-free Arctic and permafrost thawing before 0.4 Ma. If these processes continue during modern climate change, future loss of summer Arctic sea ice will accelerate the thawing of Siberian permafrost.


  
The guidance receptor plexin D1 is a mechanosensor in endothelial cells 期刊论文
NATURE, 2020, 578 (7794) : 290-+
作者:  Ma, Wenchuan;  Lutsko, James F.;  Rimer, Jeffrey D.;  Vekilov, Peter G.
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

PLXND1 is a mechanosensor that is required for endothelial cells to respond to shear stress both in vitro and in vivo by regulating the site-specific distribution of atherosclerotic lesions.


Shear stress on arteries produced by blood flow is important for vascular development and homeostasis but can also initiate atherosclerosis(1). Endothelial cells that line the vasculature use molecular mechanosensors to directly detect shear stress profiles that will ultimately lead to atheroprotective or atherogenic responses(2). Plexins are key cell-surface receptors of the semaphorin family of cell-guidance signalling proteins and can regulate cellular patterning by modulating the cytoskeleton and focal adhesion structures(3-5). However, a role for plexin proteins in mechanotransduction has not been examined. Here we show that plexin D1 (PLXND1) has a role in mechanosensation and mechanically induced disease pathogenesis. PLXND1 is required for the response of endothelial cells to shear stress in vitro and in vivo and regulates the site-specific distribution of atherosclerotic lesions. In endothelial cells, PLXND1 is a direct force sensor and forms a mechanocomplex with neuropilin-1 and VEGFR2 that is necessary and sufficient for conferring mechanosensitivity upstream of the junctional complex and integrins. PLXND1 achieves its binary functions as either a ligand or a force receptor by adopting two distinct molecular conformations. Our results establish a previously undescribed mechanosensor in endothelial cells that regulates cardiovascular pathophysiology, and provide a mechanism by which a single receptor can exhibit a binary biochemical nature.