GSTDTAP

浏览/检索结果: 共9条,第1-9条 帮助

已选(0)清除 条数/页:   排序方式:
Scientists exposed to coronavirus wonder: why weren't we notified? 期刊论文
NATURE, 2020, 579 (7800) : 480-481
作者:  Subbaraman, Nidhi
收藏  |  浏览/下载:4/0  |  提交时间:2020/07/03

US authorities are failing to test people and notify their contacts, a cornerstone of outbreak response.


Scientists exposed to coronavirus: why weren'  t we notified? US authorities are failing to test people and notify their contacts, a cornerstone of outbreak response.


  
Structural basis of DNA targeting by a transposon-encoded CRISPR-Cas system 期刊论文
NATURE, 2020, 577 (7789) : 271-+
作者:  Halpin-Healy, Tyler S.;  Klompe, Sanne E.;  Sternberg, Samuel H.;  Fernandez, Israel S.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

Bacteria use adaptive immune systems encoded by CRISPR and Cas genes to maintain genomic integrity when challenged by pathogens and mobile genetic elements(1-3). Type I CRISPR-Cas systems typically target foreign DNA for degradation via joint action of the ribonucleoprotein complex Cascade and the helicase-nuclease Cas3(4,5), but nuclease-deficient type I systems lacking Cas3 have been repurposed for RNA-guided transposition by bacterial Tn7-like transposons(6,7). How CRISPR- and transposon-associated machineries collaborate during DNA targeting and insertion remains unknown. Here we describe structures of a TniQ-Cascade complex encoded by the Vibrio cholerae Tn6677 transposon using cryo-electron microscopy, revealing the mechanistic basis of this functional coupling. The cryo-electron microscopy maps enabled de novo modelling and refinement of the transposition protein TniQ, which binds to the Cascade complex as a dimer in a head-to-tail configuration, at the interface formed by Cas6 and Cas7 near the 3'  end of the CRISPR RNA (crRNA). The natural Cas8-Cas5 fusion protein binds the 5'  crRNA handle and contacts the TniQ dimer via a flexible insertion domain. A target DNA-bound structure reveals critical interactions necessary for protospacer-adjacent motif recognition and R-loop formation. This work lays the foundation for a structural understanding of how DNA targeting by TniQ-Cascade leads to downstream recruitment of additional transposase proteins, and will guide protein engineering efforts to leverage this system for programmable DNA insertions in genome-engineering applications.


  
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.


  
General synthesis of two-dimensional van der Waals heterostructure arrays 期刊论文
NATURE, 2020: 368-+
作者:  Bloch, Joel S.;  Pesciullesi, Giorgio;  Boilevin, Jeremy;  Nosol, Kamil;  Irobalieva, Rossitza N.;  Darbre, Tamis;  Aebi, Markus;  Kossiakoff, Anthony A.;  Reymond, Jean-Louis;  Locher, Kaspar P.
收藏  |  浏览/下载:62/0  |  提交时间:2020/07/03

Two-dimensional van der Waals heterostructures (vdWHs) have attracted considerable interest(1-4). However, most vdWHs reported so far are created by an arduous micromechanical exfoliation and manual restacking process(5), which-although versatile for proof-of-concept demonstrations(6-16) and fundamental studies(17-30)-is clearly not scalable for practical technologies. Here we report a general synthetic strategy for two-dimensional vdWH arrays between metallic transition-metal dichalcogenides (m-TMDs) and semiconducting TMDs (s-TMDs). By selectively patterning nucleation sites on monolayer or bilayer s-TMDs, we precisely control the nucleation and growth of diverse m-TMDs with designable periodic arrangements and tunable lateral dimensions at the predesignated spatial locations, producing a series of vdWH arrays, including VSe2/WSe2, NiTe2/WSe2, CoTe2/WSe2, NbTe2/WSe2, VS2/WSe2, VSe2/MoS2 and VSe2/WS2. Systematic scanning transmission electron microscopy studies reveal nearly ideal vdW interfaces with widely tunable moire superlattices. With the atomically clean vdW interface, we further show that the m-TMDs function as highly reliable synthetic vdW contacts for the underlying WSe2 with excellent device performance and yield, delivering a high ON-current density of up to 900 microamperes per micrometre in bilayer WSe2 transistors. This general synthesis of diverse two-dimensional vdWH arrays provides a versatile material platform for exploring exotic physics and promises a scalable pathway to high-performance devices.


A general strategy for the synthesis of two-dimensional van der Waals heterostructure arrays is used to produce high-performance electronic devices, showing the potential of this scalable approach for practical technologies.


  
Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function 期刊论文
NATURE, 2020, 580 (7805) : 669-+
作者:  Kanarek, Naama;  Petrova, Boryana;  Sabatini, David M.
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Cryo-electron microscopy structures of the DNA-binding domains of the pioneer transcription factor SOX2 and its close homologue SOX11 elucidate the role of these factors in initiating chromatin opening and nucleosome remodelling.


'  Pioneer'  transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming(1,2). Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells(3). Here we report cryo-electron microscopy structures of the DNA-binding domains of SOX2 and its close homologue SOX11 bound to nucleosomes. The structures show that SOX factors can bind and locally distort DNA at superhelical location 2. The factors also facilitate detachment of terminal nucleosomal DNA from the histone octamer, which increases DNA accessibility. SOX-factor binding to the nucleosome can also lead to a repositioning of the N-terminal tail of histone H4 that includes residue lysine 16. We speculate that this repositioning is incompatible with higher-order nucleosome stacking, which involves contacts of the H4 tail with a neighbouring nucleosome. Our results indicate that pioneer transcription factors can use binding energy to initiate chromatin opening, and thereby facilitate nucleosome remodelling and subsequent transcription.


  
The molecular basis for sugar import in malaria parasites 期刊论文
NATURE, 2020, 578 (7794) : 321-+
作者:  Zhao, Peishen;  Liang, Yi-Lynn;  Belousoff, Matthew J.;  Deganutti, Giuseppe;  Fletcher, Madeleine M.;  Willard, Francis S.;  Bell, Michael G.;  Christe, Michael E.;  Sloop, Kyle W.;  Inoue, Asuka;  Truong, Tin T.;  Clydesdale, Lachlan;  Furness, Sebastian G. B.;  Christopoulos, Arthur;  Wang, Ming-Wei;  Miller, Laurence J.;  Reynolds, Christopher A.;  Danev, Radostin;  Sexton, Patrick M.;  Wootten, Denise
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

Elucidating the mechanism of sugar import requires a molecular understanding of how transporters couple sugar binding and gating events. Whereas mammalian glucose transporters (GLUTs) are specialists(1), the hexose transporter from the malaria parasite Plasmodium falciparum PfHT1(2,3) has acquired the ability to transport both glucose and fructose sugars as efficiently as the dedicated glucose (GLUT3) and fructose (GLUT5) transporters. Here, to establish the molecular basis of sugar promiscuity in malaria parasites, we determined the crystal structure of PfHT1 in complex with d-glucose at a resolution of 3.6 angstrom. We found that the sugar-binding site in PfHT1 is very similar to those of the distantly related GLUT3 and GLUT5 structures(4,5). Nevertheless, engineered PfHT1 mutations made to match GLUT sugar-binding sites did not shift sugar preferences. The extracellular substrate-gating helix TM7b in PfHT1 was positioned in a fully occluded conformation, providing a unique glimpse into how sugar binding and gating are coupled. We determined that polar contacts between TM7b and TM1 (located about 15 angstrom from d-glucose) are just as critical for transport as the residues that directly coordinate d-glucose, which demonstrates a strong allosteric coupling between sugar binding and gating. We conclude that PfHT1 has achieved substrate promiscuity not by modifying its sugar-binding site, but instead by evolving substrate-gating dynamics.


Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.


  
Li metal deposition and stripping in a solid-state battery via Coble creep 期刊论文
NATURE, 2020, 578 (7794) : 251-+
作者:  Helmrich, S.;  Arias, A.;  Lochead, G.;  Wintermantel, T. M.;  Buchhold, M.;  Diehl, S.;  Whitlock, S.
收藏  |  浏览/下载:56/0  |  提交时间:2020/07/03

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be(1,2) up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 10(10) MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1x excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.


By containing lithium metal within oriented tubes of a mixed ionic-electronic conductor, a 3D anode for lithium metal batteries is produced that overcomes chemomechanical stability issues at the electrolyte interface.


  
DEM Particle Fracture Model 科技报告
来源:US Department of Energy (DOE). 出版年: 2015
作者:  Zhang, Boning;  Herbold, Eric B.;  Homel, Michael A.;  Regueiro, Richard A.
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/05
Discrete Element Method  particle fracture model  high strain rate  split Hopkinson pressure bar experiments  Hoek-Brown fracture criterion  maximum tensile stress in contacts  packing e#11  ects  
Clean Cities Program Contacts (Fact Sheet) 科技报告
来源:US Department of Energy (DOE). 出版年: 2013
作者:  [null]
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/05
CLEAN CITIES  COALITIONS  CONTACTS  FLEETS  ALTERNATIVE FUELS