1. Thermal vesiculation during volcanic eruptions.
作者: Yan Lavallée.;Donald B Dingwell.;Jeffrey B Johnson.;Corrado Cimarelli.;Adrian J Hornby.;Jackie E Kendrick.;Felix W von Aulock.;Ben M Kennedy.;Benjamin J Andrews.;Fabian B Wadsworth.;Emma Rhodes.;Gustavo Chigna.
来源: Nature. 2015年528卷7583期544-7页
Terrestrial volcanic eruptions are the consequence of magmas ascending to the surface of the Earth. This ascent is driven by buoyancy forces, which are enhanced by bubble nucleation and growth (vesiculation) that reduce the density of magma. The development of vesicularity also greatly reduces the 'strength' of magma, a material parameter controlling fragmentation and thus the explosive potential of the liquid rock. The development of vesicularity in magmas has until now been viewed (both thermodynamically and kinetically) in terms of the pressure dependence of the solubility of water in the magma, and its role in driving gas saturation, exsolution and expansion during decompression. In contrast, the possible effects of the well documented negative temperature dependence of solubility of water in magma has largely been ignored. Recently, petrological constraints have demonstrated that considerable heating of magma may indeed be a common result of the latent heat of crystallization as well as viscous and frictional heating in areas of strain localization. Here we present field and experimental observations of magma vesiculation and fragmentation resulting from heating (rather than decompression). Textural analysis of volcanic ash from Santiaguito volcano in Guatemala reveals the presence of chemically heterogeneous filaments hosting micrometre-scale vesicles. The textures mirror those developed by disequilibrium melting induced via rapid heating during fault friction experiments, demonstrating that friction can generate sufficient heat to induce melting and vesiculation of hydrated silicic magma. Consideration of the experimentally determined temperature and pressure dependence of water solubility in magma reveals that, for many ascent paths, exsolution may be more efficiently achieved by heating than by decompression. We conclude that the thermal path experienced by magma during ascent strongly controls degassing, vesiculation, magma strength and the effusive-explosive transition in volcanic eruptions.
2. Processing and properties of magnesium containing a dense uniform dispersion of nanoparticles.
作者: Lian-Yi Chen.;Jia-Quan Xu.;Hongseok Choi.;Marta Pozuelo.;Xiaolong Ma.;Sanjit Bhowmick.;Jenn-Ming Yang.;Suveen Mathaudhu.;Xiao-Chun Li.
来源: Nature. 2015年528卷7583期539-43页
Magnesium is a light metal, with a density two-thirds that of aluminium, is abundant on Earth and is biocompatible; it thus has the potential to improve energy efficiency and system performance in aerospace, automobile, defence, mobile electronics and biomedical applications. However, conventional synthesis and processing methods (alloying and thermomechanical processing) have reached certain limits in further improving the properties of magnesium and other metals. Ceramic particles have been introduced into metal matrices to improve the strength of the metals, but unfortunately, ceramic microparticles severely degrade the plasticity and machinability of metals, and nanoparticles, although they have the potential to improve strength while maintaining or even improving the plasticity of metals, are difficult to disperse uniformly in metal matrices. Here we show that a dense uniform dispersion of silicon carbide nanoparticles (14 per cent by volume) in magnesium can be achieved through a nanoparticle self-stabilization mechanism in molten metal. An enhancement of strength, stiffness, plasticity and high-temperature stability is simultaneously achieved, delivering a higher specific yield strength and higher specific modulus than almost all structural metals.
3. Single-chip microprocessor that communicates directly using light.
作者: Chen Sun.;Mark T Wade.;Yunsup Lee.;Jason S Orcutt.;Luca Alloatti.;Michael S Georgas.;Andrew S Waterman.;Jeffrey M Shainline.;Rimas R Avizienis.;Sen Lin.;Benjamin R Moss.;Rajesh Kumar.;Fabio Pavanello.;Amir H Atabaki.;Henry M Cook.;Albert J Ou.;Jonathan C Leu.;Yu-Hsin Chen.;Krste Asanović.;Rajeev J Ram.;Miloš A Popović.;Vladimir M Stojanović.
来源: Nature. 2015年528卷7583期534-8页
Data transport across short electrical wires is limited by both bandwidth and power density, which creates a performance bottleneck for semiconductor microchips in modern computer systems--from mobile phones to large-scale data centres. These limitations can be overcome by using optical communications based on chip-scale electronic-photonic systems enabled by silicon-based nanophotonic devices. However, combining electronics and photonics on the same chip has proved challenging, owing to microchip manufacturing conflicts between electronics and photonics. Consequently, current electronic-photonic chips are limited to niche manufacturing processes and include only a few optical devices alongside simple circuits. Here we report an electronic-photonic system on a single chip integrating over 70 million transistors and 850 photonic components that work together to provide logic, memory, and interconnect functions. This system is a realization of a microprocessor that uses on-chip photonic devices to directly communicate with other chips using light. To integrate electronics and photonics at the scale of a microprocessor chip, we adopt a 'zero-change' approach to the integration of photonics. Instead of developing a custom process to enable the fabrication of photonics, which would complicate or eliminate the possibility of integration with state-of-the-art transistors at large scale and at high yield, we design optical devices using a standard microelectronics foundry process that is used for modern microprocessors. This demonstration could represent the beginning of an era of chip-scale electronic-photonic systems with the potential to transform computing system architectures, enabling more powerful computers, from network infrastructure to data centres and supercomputers.
4. Quantum superposition at the half-metre scale.
作者: T Kovachy.;P Asenbaum.;C Overstreet.;C A Donnelly.;S M Dickerson.;A Sugarbaker.;J M Hogan.;M A Kasevich.
来源: Nature. 2015年528卷7583期530-3页
The quantum superposition principle allows massive particles to be delocalized over distant positions. Though quantum mechanics has proved adept at describing the microscopic world, quantum superposition runs counter to intuitive conceptions of reality and locality when extended to the macroscopic scale, as exemplified by the thought experiment of Schrödinger's cat. Matter-wave interferometers, which split and recombine wave packets in order to observe interference, provide a way to probe the superposition principle on macroscopic scales and explore the transition to classical physics. In such experiments, large wave-packet separation is impeded by the need for long interaction times and large momentum beam splitters, which cause susceptibility to dephasing and decoherence. Here we use light-pulse atom interferometry to realize quantum interference with wave packets separated by up to 54 centimetres on a timescale of 1 second. These results push quantum superposition into a new macroscopic regime, demonstrating that quantum superposition remains possible at the distances and timescales of everyday life. The sub-nanokelvin temperatures of the atoms and a compensation of transverse optical forces enable a large separation while maintaining an interference contrast of 28 per cent. In addition to testing the superposition principle in a new regime, large quantum superposition states are vital to exploring gravity with atom interferometers in greater detail. We anticipate that these states could be used to increase sensitivity in tests of the equivalence principle, measure the gravitational Aharonov-Bohm effect, and eventually detect gravitational waves and phase shifts associated with general relativity.
5. A dynamic magnetic tension force as the cause of failed solar eruptions.
作者: Clayton E Myers.;Masaaki Yamada.;Hantao Ji.;Jongsoo Yoo.;William Fox.;Jonathan Jara-Almonte.;Antonia Savcheva.;Edward E DeLuca.
来源: Nature. 2015年528卷7583期526-9页
Coronal mass ejections are solar eruptions driven by a sudden release of magnetic energy stored in the Sun's corona. In many cases, this magnetic energy is stored in long-lived, arched structures called magnetic flux ropes. When a flux rope destabilizes, it can either erupt and produce a coronal mass ejection or fail and collapse back towards the Sun. The prevailing belief is that the outcome of a given event is determined by a magnetohydrodynamic force imbalance called the torus instability. This belief is challenged, however, by observations indicating that torus-unstable flux ropes sometimes fail to erupt. This contradiction has not yet been resolved because of a lack of coronal magnetic field measurements and the limitations of idealized numerical modelling. Here we report the results of a laboratory experiment that reveal a previously unknown eruption criterion below which torus-unstable flux ropes fail to erupt. We find that such 'failed torus' events occur when the guide magnetic field (that is, the ambient field that runs toroidally along the flux rope) is strong enough to prevent the flux rope from kinking. Under these conditions, the guide field interacts with electric currents in the flux rope to produce a dynamic toroidal field tension force that halts the eruption. This magnetic tension force is missing from existing eruption models, which is why such models cannot explain or predict failed torus events.
6. Insulator dysfunction and oncogene activation in IDH mutant gliomas.
作者: William A Flavahan.;Yotam Drier.;Brian B Liau.;Shawn M Gillespie.;Andrew S Venteicher.;Anat O Stemmer-Rachamimov.;Mario L Suvà.;Bradley E Bernstein.
来源: Nature. 2016年529卷7584期110-4页
Gain-of-function IDH mutations are initiating events that define major clinical and prognostic classes of gliomas. Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5'-methylcytosine hydroxylases. TET enzymes catalyse a key step in the removal of DNA methylation. IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP), although the functional importance of this altered epigenetic state remains unclear. Here we show that human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein. Reduced CTCF binding is associated with loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to interact aberrantly with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with a demethylating agent partially restores insulator function and downregulates PDGFRA. Conversely, CRISPR-mediated disruption of the CTCF motif in IDH wild-type gliomaspheres upregulates PDGFRA and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.
7. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens.
作者: Joshua Tan.;Kathrin Pieper.;Luca Piccoli.;Abdirahman Abdi.;Mathilde Foglierini Perez.;Roger Geiger.;Claire Maria Tully.;David Jarrossay.;Francis Maina Ndungu.;Juliana Wambua.;Philip Bejon.;Chiara Silacci Fregni.;Blanca Fernandez-Rodriguez.;Sonia Barbieri.;Siro Bianchi.;Kevin Marsh.;Vandana Thathy.;Davide Corti.;Federica Sallusto.;Peter Bull.;Antonio Lanzavecchia.
来源: Nature. 2016年529卷7584期105-109页
Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 98 amino acid collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B-cell clone and carry distinct somatic mutations in the LAIR1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.
8. Cancer: Oncogene brought into the loop.
Analysis of the 3D structure of DNA in tumour cells reveals how mutations in the IDH1 gene, and associated changes in methyl groups attached to DNA, elevate the expression of cancer-promoting genes.
9. The global spectrum of plant form and function.
作者: Sandra Díaz.;Jens Kattge.;Johannes H C Cornelissen.;Ian J Wright.;Sandra Lavorel.;Stéphane Dray.;Björn Reu.;Michael Kleyer.;Christian Wirth.;I Colin Prentice.;Eric Garnier.;Gerhard Bönisch.;Mark Westoby.;Hendrik Poorter.;Peter B Reich.;Angela T Moles.;John Dickie.;Andrew N Gillison.;Amy E Zanne.;Jérôme Chave.;S Joseph Wright.;Serge N Sheremet'ev.;Hervé Jactel.;Christopher Baraloto.;Bruno Cerabolini.;Simon Pierce.;Bill Shipley.;Donald Kirkup.;Fernando Casanoves.;Julia S Joswig.;Angela Günther.;Valeria Falczuk.;Nadja Rüger.;Miguel D Mahecha.;Lucas D Gorné.
来源: Nature. 2016年529卷7585期167-71页
Earth is home to a remarkable diversity of plant forms and life histories, yet comparatively few essential trait combinations have proved evolutionarily viable in today's terrestrial biosphere. By analysing worldwide variation in six major traits critical to growth, survival and reproduction within the largest sample of vascular plant species ever compiled, we found that occupancy of six-dimensional trait space is strongly concentrated, indicating coordination and trade-offs. Three-quarters of trait variation is captured in a two-dimensional global spectrum of plant form and function. One major dimension within this plane reflects the size of whole plants and their parts; the other represents the leaf economics spectrum, which balances leaf construction costs against growth potential. The global plant trait spectrum provides a backdrop for elucidating constraints on evolution, for functionally qualifying species and ecosystems, and for improving models that predict future vegetation based on continuous variation in plant form and function.
10. Controlling many-body states by the electric-field effect in a two-dimensional material.
作者: L J Li.;E C T O'Farrell.;K P Loh.;G Eda.;B Özyilmaz.;A H Castro Neto.
来源: Nature. 2016年529卷7585期185-9页
To understand the complex physics of a system with strong electron-electron interactions, the ideal is to control and monitor its properties while tuning an external electric field applied to the system (the electric-field effect). Indeed, complete electric-field control of many-body states in strongly correlated electron systems is fundamental to the next generation of condensed matter research and devices. However, the material must be thin enough to avoid shielding of the electric field in the bulk material. Two-dimensional materials do not experience electrical screening, and their charge-carrier density can be controlled by gating. Octahedral titanium diselenide (1T-TiSe2) is a prototypical two-dimensional material that reveals a charge-density wave (CDW) and superconductivity in its phase diagram, presenting several similarities with other layered systems such as copper oxides, iron pnictides, and crystals of rare-earth elements and actinide atoms. By studying 1T-TiSe2 single crystals with thicknesses of 10 nanometres or less, encapsulated in two-dimensional layers of hexagonal boron nitride, we achieve unprecedented control over the CDW transition temperature (tuned from 170 kelvin to 40 kelvin), and over the superconductivity transition temperature (tuned from a quantum critical point at 0 kelvin up to 3 kelvin). Electrically driving TiSe2 over different ordered electronic phases allows us to study the details of the phase transitions between many-body states. Observations of periodic oscillations of magnetoresistance induced by the Little-Parks effect show that the appearance of superconductivity is directly correlated with the spatial texturing of the amplitude and phase of the superconductivity order parameter, corresponding to a two-dimensional matrix of superconductivity. We infer that this superconductivity matrix is supported by a matrix of incommensurate CDW states embedded in the commensurate CDW states. Our results show that spatially modulated electronic states are fundamental to the appearance of two-dimensional superconductivity.
11. Plant functional traits have globally consistent effects on competition.
作者: Georges Kunstler.;Daniel Falster.;David A Coomes.;Francis Hui.;Robert M Kooyman.;Daniel C Laughlin.;Lourens Poorter.;Mark Vanderwel.;Ghislain Vieilledent.;S Joseph Wright.;Masahiro Aiba.;Christopher Baraloto.;John Caspersen.;J Hans C Cornelissen.;Sylvie Gourlet-Fleury.;Marc Hanewinkel.;Bruno Herault.;Jens Kattge.;Hiroko Kurokawa.;Yusuke Onoda.;Josep Peñuelas.;Hendrik Poorter.;Maria Uriarte.;Sarah Richardson.;Paloma Ruiz-Benito.;I-Fang Sun.;Göran Ståhl.;Nathan G Swenson.;Jill Thompson.;Bertil Westerlund.;Christian Wirth.;Miguel A Zavala.;Hongcheng Zeng.;Jess K Zimmerman.;Niklaus E Zimmermann.;Mark Westoby.
来源: Nature. 2016年529卷7585期204-7页
Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions, but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear. Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits--wood density, specific leaf area and maximum height--consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies. Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.
12. Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function.
作者: Elaine E Storm.;Steffen Durinck.;Felipe de Sousa e Melo.;Jarrod Tremayne.;Noelyn Kljavin.;Christine Tan.;Xiaofen Ye.;Cecilia Chiu.;Thinh Pham.;Jo-Anne Hongo.;Travis Bainbridge.;Ron Firestein.;Elizabeth Blackwood.;Ciara Metcalfe.;Eric W Stawiski.;Robert L Yauch.;Yan Wu.;Frederic J de Sauvage.
来源: Nature. 2016年529卷7584期97-100页
Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
13. SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination.
作者: Dorothy Yanling Zhao.;Gerald Gish.;Ulrich Braunschweig.;Yue Li.;Zuyao Ni.;Frank W Schmitges.;Guoqing Zhong.;Ke Liu.;Weiguo Li.;Jason Moffat.;Masoud Vedadi.;Jinrong Min.;Tony J Pawson.;Benjamin J Blencowe.;Jack F Greenblatt.
来源: Nature. 2016年529卷7584期48-53页
The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA-DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.
14. Rapid removal of organic micropollutants from water by a porous β-cyclodextrin polymer.
作者: Alaaeddin Alsbaiee.;Brian J Smith.;Leilei Xiao.;Yuhan Ling.;Damian E Helbling.;William R Dichtel.
来源: Nature. 2016年529卷7585期190-4页
The global occurrence in water resources of organic micropollutants, such as pesticides and pharmaceuticals, has raised concerns about potential negative effects on aquatic ecosystems and human health. Activated carbons are the most widespread adsorbent materials used to remove organic pollutants from water but they have several deficiencies, including slow pollutant uptake (of the order of hours) and poor removal of many relatively hydrophilic micropollutants. Furthermore, regenerating spent activated carbon is energy intensive (requiring heating to 500-900 degrees Celsius) and does not fully restore performance. Insoluble polymers of β-cyclodextrin, an inexpensive, sustainably produced macrocycle of glucose, are likewise of interest for removing micropollutants from water by means of adsorption. β-cyclodextrin is known to encapsulate pollutants to form well-defined host-guest complexes, but until now cross-linked β-cyclodextrin polymers have had low surface areas and poor removal performance compared to conventional activated carbons. Here we crosslink β-cyclodextrin with rigid aromatic groups, providing a high-surface-area, mesoporous polymer of β-cyclodextrin. It rapidly sequesters a variety of organic micropollutants with adsorption rate constants 15 to 200 times greater than those of activated carbons and non-porous β-cyclodextrin adsorbent materials. In addition, the polymer can be regenerated several times using a mild washing procedure with no loss in performance. Finally, the polymer outperformed a leading activated carbon for the rapid removal of a complex mixture of organic micropollutants at environmentally relevant concentrations. These findings demonstrate the promise of porous cyclodextrin-based polymers for rapid, flow-through water treatment.
15. Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site.
Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer-Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon-oxygen bonds and generate carbon-carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl-diphosphine ligand, that activates and cleaves the strong carbon-oxygen bond of carbon monoxide, enacts carbon-carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl-diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site.
16. Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.
作者: Jiangtao Guo.;Weizhong Zeng.;Qingfeng Chen.;Changkeun Lee.;Liping Chen.;Yi Yang.;Chunlei Cang.;Dejian Ren.;Youxing Jiang.
来源: Nature. 2016年531卷7593期196-201页
Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here we present the crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca(2+). Ca(2+) binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain, the conformational changes of which are coupled to the pair of inner helices from the second 6-TM domains. Luminal Ca(2+) or Ba(2+) can modulate voltage activation by stabilizing the second voltage-sensing domain in the resting state and shift voltage activation towards more positive potentials. Our Ba(2+)-bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels.
17. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit.
Parasitic helminths and allergens induce a type 2 immune response leading to profound changes in tissue physiology, including hyperplasia of mucus-secreting goblet cells and smooth muscle hypercontractility. This response, known as 'weep and sweep', requires interleukin (IL)-13 production by tissue-resident group 2 innate lymphoid cells (ILC2s) and recruited type 2 helper T cells (TH2 cells). Experiments in mice and humans have demonstrated requirements for the epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 in the activation of ILC2s, but the sources and regulation of these signals remain poorly defined. In the small intestine, the epithelium consists of at least five distinct cellular lineages, including the tuft cell, whose function is unclear. Here we show that tuft cells constitutively express IL-25 to sustain ILC2 homeostasis in the resting lamina propria in mice. After helminth infection, tuft-cell-derived IL-25 further activates ILC2s to secrete IL-13, which acts on epithelial crypt progenitors to promote differentiation of tuft and goblet cells, leading to increased frequencies of both. Tuft cells, ILC2s and epithelial progenitors therefore comprise a response circuit that mediates epithelial remodelling associated with type 2 immunity in the small intestine, and perhaps at other mucosal barriers populated by these cells.
18. Rational design of α-helical tandem repeat proteins with closed architectures.
作者: Lindsey Doyle.;Jazmine Hallinan.;Jill Bolduc.;Fabio Parmeggiani.;David Baker.;Barry L Stoddard.;Philip Bradley.
来源: Nature. 2015年528卷7583期585-8页
Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks. The overall architecture of tandem repeat protein structures--which is dictated by the internal geometry and local packing of the repeat building blocks--is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed α-solenoid repeat structures (α-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the amino (N) and carboxy (C) termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed α-solenoid repeats with a left-handed helical architecture that--to our knowledge--is not yet present in the protein structure database.
19. Competition between DNA methylation and transcription factors determines binding of NRF1.
作者: Silvia Domcke.;Anaïs Flore Bardet.;Paul Adrian Ginno.;Dominik Hartl.;Lukas Burger.;Dirk Schübeler.
来源: Nature. 2015年528卷7583期575-9页
Eukaryotic transcription factors (TFs) are key determinants of gene activity, yet they bind only a fraction of their corresponding DNA sequence motifs in any given cell type. Chromatin has the potential to restrict accessibility of binding sites; however, in which context chromatin states are instructive for TF binding remains mainly unknown. To explore the contribution of DNA methylation to constrained TF binding, we mapped DNase-I-hypersensitive sites in murine stem cells in the presence and absence of DNA methylation. Methylation-restricted sites are enriched for TF motifs containing CpGs, especially for those of NRF1. In fact, the TF NRF1 occupies several thousand additional sites in the unmethylated genome, resulting in increased transcription. Restoring de novo methyltransferase activity initiates remethylation at these sites and outcompetes NRF1 binding. This suggests that binding of DNA-methylation-sensitive TFs relies on additional determinants to induce local hypomethylation. In support of this model, removal of neighbouring motifs in cis or of a TF in trans causes local hypermethylation and subsequent loss of NRF1 binding. This competition between DNA methylation and TFs in vivo reveals a case of cooperativity between TFs that acts indirectly via DNA methylation. Methylation removal by methylation-insensitive factors enables occupancy of methylation-sensitive factors, a principle that rationalizes hypomethylation of regulatory regions.
20. A continuum from clear to cloudy hot-Jupiter exoplanets without primordial water depletion.
作者: David K Sing.;Jonathan J Fortney.;Nikolay Nikolov.;Hannah R Wakeford.;Tiffany Kataria.;Thomas M Evans.;Suzanne Aigrain.;Gilda E Ballester.;Adam S Burrows.;Drake Deming.;Jean-Michel Désert.;Neale P Gibson.;Gregory W Henry.;Catherine M Huitson.;Heather A Knutson.;Alain Lecavelier des Etangs.;Frederic Pont.;Adam P Showman.;Alfred Vidal-Madjar.;Michael H Williamson.;Paul A Wilson.
来源: Nature. 2016年529卷7584期59-62页
Thousands of transiting exoplanets have been discovered, but spectral analysis of their atmospheres has so far been dominated by a small number of exoplanets and data spanning relatively narrow wavelength ranges (such as 1.1-1.7 micrometres). Recent studies show that some hot-Jupiter exoplanets have much weaker water absorption features in their near-infrared spectra than predicted. The low amplitude of water signatures could be explained by very low water abundances, which may be a sign that water was depleted in the protoplanetary disk at the planet's formation location, but it is unclear whether this level of depletion can actually occur. Alternatively, these weak signals could be the result of obscuration by clouds or hazes, as found in some optical spectra. Here we report results from a comparative study of ten hot Jupiters covering the wavelength range 0.3-5 micrometres, which allows us to resolve both the optical scattering and infrared molecular absorption spectroscopically. Our results reveal a diverse group of hot Jupiters that exhibit a continuum from clear to cloudy atmospheres. We find that the difference between the planetary radius measured at optical and infrared wavelengths is an effective metric for distinguishing different atmosphere types. The difference correlates with the spectral strength of water, so that strong water absorption lines are seen in clear-atmosphere planets and the weakest features are associated with clouds and hazes. This result strongly suggests that primordial water depletion during formation is unlikely and that clouds and hazes are the cause of weaker spectral signatures.
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