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Scientists— just like everybody else — have little idea what will happen now that the United Kingdom has voted to exit the European Union.
Problems of modern society demand collaborative research.
The perils of the past must not be allowed to happen again
Major reform of education in India should encourage original thinking to boost the nation's research, argues Anurag Chaurasia.
Mammals, birds and reptiles inherited key cell structures that give rise to their fur, feathers and scales from a shared reptilian ancestor.Scientists have long debated whether these skin appendages evolved independently or had a single origin. To find out, Nicolas Di-Poï and Michel Milinkovitch
Inexpensive fast-growing plants have been transformed into factories that churn out an important antimalarial drug.Artemisinin is the only proven malaria treatment, with hundreds of millions of doses taken every year. The sweet wormwood plant (Artemisia annua) produces a precursor of the compound,
The cells in the retina that enable night vision may have evolved from those that sense colour.Typically, most of the light-sensing cells in mammalian retinas are rod cells, which are sensitive in low light. However, vertebrate ancestors only had cells resembling cones, which function
A membrane with nanometre-sized pores can capture low levels of heat energy to generate power.Industrial plants are abundant sources of waste heat, but the relatively small temperature difference between the source (which is usually below 100°C) and its surroundings makes it hard to
Bites from mosquitoes that spread viruses trigger a distinct immune response in the skin after they bite, which increases the severity of infection caused by the transmitted virus.Clive McKimmie at the University of Leeds, UK, and his colleagues injected mice with one of two
Like humans, some monkeys show declining social activity with age.Laura Almeling at the German Primate Center in Göttingen, Germany, and her colleagues studied Barbary macaques (Macaca sylvanus; pictured), and found that older females spent less time grooming others and interacted with
Some trees in Africa already seem to be adapting to the warming climate by using water more efficiently.Iain Robertson of Swansea University, UK, and his colleagues collected a small number of samples from three tree species in Ethiopia, Namibia and South Africa, covering a
A cancer therapy that uses genetically modified versions of patients' immune cells to treat blood cancers has been adapted to attack solid human tumours implanted into mice.Engineered T cells are designed to home in on specific proteins on the surface of cancer cells in
A rare fish species living in an isolated cavern pool probably originated when the cavern first opened to the surface around 60,000 years ago.The Devils Hole pupfish (Cyprinodon diabolis) is one of the world's rarest animals, and researchers debate whether humans introduced
A bilayered material can curl itself into a cylinder in response to a stimulus, mimicking the leaves of the plant Mimosa pudica, which quickly fold up when lightly touched (pictured).Zuankai Wang at the City University of Hong Kong, Antonio Tricoli at
Ill workers rescued from Antarctic station; controversial surgeon Paolo Macchiarini faces manslaughter charges; and China dominates list of fastest supercomputers.
Researchers organize to lobby for science as country prepares for life outside the EU.
The mission will peek through the gas giant’s swirling clouds in search of a planetary core.
Cooler, cloudier summers slow snowmelt in Himalayas
Users urge caution in revamp of service at the heart of physics.
From incubation in a bra to an afterlife under glass, how a cloned sheep attained celebrity status.
Strange signals are bombarding Earth. But where are they coming from?
Stéphane Hallegatte, Katharine J. Mach and colleagues urge researchers to gear their studies, and the way they present their results, to the needs of policymakers.
Marc Fleurbaey and colleagues explain why and how 300 scholars in the social sciences and humanities are collaborating to synthesize knowledge for policymakers.
Ann Finkbeiner examines a study that probes how drones have 'remixed' warfare.
Barbara Kiser reviews five of the week's best science picks.
Colin Macilwain talks to the curators of the National Museum of Scotland on the eve of a grand expansion.
The race to describe and archive the planet's dwindling biodiversity (see K.-D. B.DijkstraNature533, 172–174;10.1038/533172a2016) becomes even more urgent with the realization that the task's scale may be an order of magnitude greater than estimated.Dijkstra
Daniel Sarewitz argues that the pressure to publish is fuelling irreproducibility, but we disagree that the solution is to publish fewer papers (Nature533, 147;10.1038/533147a2016). In today's competitive arena, asking this of scientists— particularly junior ones — is
As appointed representatives of the European Union's Scientific Forum on Invasive Alien Species, we wish to point out that the EU regulation states priority should be given to the listing of invasive species“that are not yet present in the Union or are at an
Israel's Weizmann Institute of Science is ranked among the world's top research institutions, but only 16.5% of its faculty members are women. Although this is still too low for a multidisciplinary institution, a series of initiatives are gradually redressing the balance.In Israel, common hurdles
Launching satellites to measure carbon dioxide emissions is only part of a more integrated solution to achieving the goals of the Paris climate agreement (Nature533, 446–447;10.1038/533446a2016). In our view, the biggest hurdle is to reduce the
Theoretical physicist and Higgs-boson pioneer.
Looking for funding? Here's a smart guide for sources off the beaten track, says Ingrid Eisenstadter.
Time to take stock.
The science-workforce graph in‘China by the Numbers’ (Nature534, 452–453; 2016) erred in stating that China’s population is 1.3 trillion. It is more than 1.3 billion.
Interactions in the gut between host cells and bacteria can determine a state of health or disease. A study investigates how antibiotic treatment can affect host cells in a way that drives growth of pathogenic bacteria. See Letter p.697
Two studies reveal that early-life malfunction in organelles called mitochondria brings about lasting changes in how DNA is packaged. These alterations have consequences for cellular stress responses and organismal longevity.
Decoded and precisely dated information encrypted in stalagmites from a cave in China reveal past climatic changes and provide insight into the complex interactions in today's climate system. See Letter p.640
50 Years AgoAtlantic tunas will share with whales some immunity from hunting as a result of a convention on conservation drafted ... by the representatives of seventeen nations ... The convention has been prompted by evidence in recent years that more boats are chasing
In some species, cancer cells can be directly transmitted between individuals. An analysis in shellfish now shows that some transmissible cancers can even cross the species barrier. See Letter p.705
The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to“pursue efforts” to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess
Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record’s length and temporal
Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as
In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos
Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed. The precise ages of meteorites indicate that planetesimals—the building blocks of planets—are produced within the first million years of a star’s life. Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration. Other theories posit that planet assembly at small orbital separations may be common. Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5–10 million years old and has a tenuous dust disk extending outward from about twice the Earth–Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth–Sun separation.
Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star. It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks, or later, once multiple planets are formed and interact. Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars, whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planet–disk interactions.
Spin models are the prime example of simplified many-body Hamiltonians used to model complex, strongly correlated real-world materials. However, despite the simplified character of such models, their dynamics often cannot be simulated exactly on classical computers when the number of particles exceeds a few tens. For this reason, quantum simulation of spin Hamiltonians using the tools of atomic and molecular physics has become a very active field over the past years, using ultracold atoms or molecules in optical lattices, or trapped ions. All of these approaches have their own strengths and limitations. Here we report an alternative platform for the study of spin systems, using individual atoms trapped in tunable two-dimensional arrays of optical microtraps with arbitrary geometries, where filling fractions range from 60 to 100 per cent. When excited to high-energy Rydberg D states, the atoms undergo strong interactions whose anisotropic character opens the way to simulating exotic matter. We illustrate the versatility of our system by studying the dynamics of a quantum Ising-like spin-1/2 system in a transverse field with up to 30 spins, for a variety of geometries in one and two dimensions, and for a wide range of interaction strengths. For geometries where the anisotropy is expected to have small effects on the dynamics, we find excellent agreement with ab initio simulations of the spin-1/2 system, while for strongly anisotropic situations the multilevel structure of the D states has a measurable influence. Our findings establish arrays of single Rydberg atoms as a versatile platform for the study of quantum magnetism.
Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock–Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen–Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons.
When a gecko moves on a ceiling it makes use of adhesion and stiction. Stiction—static friction—is experienced on microscopic and macroscopic scales and is related to adhesion and sliding friction. Although important for most locomotive processes, the concepts of adhesion, stiction and sliding friction are often only empirically correlated. A more detailed understanding of these concepts will, for example, help to improve the design of increasingly smaller devices such as micro- and nanoelectromechanical switches. Here we show how stiction and adhesion are related for a liquid drop on a hexagonal boron nitride monolayer on rhodium, by measuring dynamic contact angles in two distinct states of the solid–liquid interface: a corrugated state in the absence of hydrogen intercalation and an intercalation-induced flat state. Stiction and adhesion can be reversibly switched by applying different electrochemical potentials to the sample, causing atomic hydrogen to be intercalated or not. We ascribe the change in adhesion to a change in lateral electric field of in-plane two-nanometre dipole rings, because it cannot be explained by the change in surface roughness known from the Wenzel model. Although the change in adhesion can be calculated for the system we study, it is not yet possible to determine the stiction at such a solid–liquid interface using ab initio methods. The inorganic hybrid of hexagonal boron nitride and rhodium is very stable and represents a new class of switchable surfaces with the potential for application in the study of adhesion, friction and lubrication.
Terrestrial ecosystems currently offset one-quarter of anthropogenic carbon dioxide (CO2) emissions because of a slight imbalance between global terrestrial photosynthesis and respiration. Understanding what controls these two biological fluxes is therefore crucial to predicting climate change. Yet there is no way of directly measuring the photosynthesis or daytime respiration of a whole ecosystem of interacting organisms; instead, these fluxes are generally inferred from measurements of net ecosystem–atmosphere CO2 exchange (NEE), in a way that is based on assumed ecosystem-scale responses to the environment. The consequent view of temperate deciduous forests (an important CO2 sink) is that, first, ecosystem respiration is greater during the day than at night; and second, ecosystem photosynthetic light-use efficiency peaks after leaf expansion in spring and then declines, presumably because of leaf ageing or water stress. This view has underlain the development of terrestrial biosphere models used in climate prediction and of remote sensing indices of global biosphere productivity. Here, we use new isotopic instrumentation to determine ecosystem photosynthesis and daytime respiration in a temperate deciduous forest over a three-year period. We find that ecosystem respiration is lower during the day than at night—the first robust evidence of the inhibition of leaf respiration bylight at the ecosystem scale. Because they do not capture this effect, standard approaches overestimate ecosystem photosynthesis and daytime respiration in the first half of the growing season at our site, and inaccurately portray ecosystem photosynthetic light-use efficiency. These findings reviseour understanding of forest–atmosphere carbon exchange, and provide a basis for investigating how leaf-level physiological dynamics manifest at the canopy scale in other ecosystems.
Interdisciplinary research is widely considered a hothouse for innovation, and the only plausible approach to complex problems such as climate change. One barrier to interdisciplinary research is the widespread perception that interdisciplinary projects are less likely to be funded than those with a narrower focus. However, this commonly held belief has been difficult to evaluate objectively, partly because of lack of a comparable, quantitative measure of degree of interdisciplinarity that can be applied to funding application data. Here we compare the degree to which research proposals span disparate fields by using a biodiversity metric that captures the relative representation of different fields (balance) and their degree of difference (disparity). The Australian Research Council’s Discovery Programme provides an ideal test case, because a single annual nationwide competitive grants scheme covers fundamental research in all disciplines, including arts, humanities and sciences. Using data on all 18,476 proposals submitted to the scheme over 5 consecutive years, including successful and unsuccessful applications, we show that the greater the degree of interdisciplinarity, the lower the probability of being funded. The negative impact of interdisciplinarity is significant even when number of collaborators, primary research field and type of institution are taken into account. This is the first broad-scale quantitative assessment of success rates of interdisciplinary research proposals. The interdisciplinary distance metric allows efficient evaluation of trends in research funding, and could be used to identify proposals that require assessment strategies appropriate to interdisciplinary research.
Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF–lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF–lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-pairedcontext. Finally, we show that altering inhibitory transmission at BF–lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF–lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.
In 1943, Luria and Delbrück used a phage-resistance assay to establish spontaneous mutation as a driving force of microbial diversity. Mutation rates are still studied using such assays, but these can only be used to examine the small minority of mutations conferring survival in a particular condition. Newer approaches, such as long-term evolution followed by whole-genome sequencing, may be skewed by mutational ‘hot’ or ‘cold’ spots. Both approaches are affected by numerous caveats. Here we devise a method, maximum-depth sequencing (MDS), to detect extremely rare variants in a population of cells through error-corrected, high-throughput sequencing. We directly measure locus-specific mutation rates in Escherichia coli and show that they vary across the genome by at least an order of magnitude. Our data suggest that certain types of nucleotide misincorporation occur 104-fold more frequently than the basal rate of mutations, but are repaired in vivo. Our data also suggest specific mechanisms of antibiotic-induced mutagenesis, including downregulation of mismatch repair via oxidative stress, transcription–replication conflicts, and, in the case of fluoroquinolones, direct damage to DNA.
Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars, increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse. These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel. However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion.
Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease and non-compaction cardiomyopathies, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form.
Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils and dogs), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria) suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers are found spreading within the species of origin, cross-species transmission of cancer cells can occur.
The mitochondrial matrix is unique in that it must integrate the folding and assembly of proteins derived from the nuclear and mitochondrial genomes. In Caenorhabditis elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial-matrix-localized ornithine transcarbamylase induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 (ref. 8) or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response encompasses widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing caused by transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3 (ref. 10). This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.
After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL–MMS22L binds new histones H3–H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.
A fraction of ribosomes engaged in translation will fail to terminate when reaching a stop codon, yielding nascent proteins inappropriately extended on their C termini. Although such extended proteins can interfere with normal cellular processes, known mechanisms of translational surveillance are insufficient to protect cells from potential dominant consequences. Here, through a combination of transgenics and CRISPR–Cas9 gene editing in Caenorhabditis elegans, we demonstrate a consistent ability of cells to block accumulation of C-terminal-extended proteins that result from failure to terminate at stop codons. Sequences encoded by the 3′ untranslated region (UTR) were sufficient to lower protein levels. Measurements of mRNA levels and translation suggested a co- or post-translational mechanism of action for these sequences in C. elegans. Similar mechanisms evidently operate in human cells, in which we observed a comparable tendency for translated human 3′ UTR sequences to reduce mature protein expression in tissue culture assays, including 3′ UTR sequences from the hypomorphic ‘Constant Spring’ haemoglobin stop codon variant. We suggest that 3′ UTRs may encode peptide sequences that destabilize the attached protein, providing mitigation of unwelcome and varied translation errors.
The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. The energy for these movements is generated during a complex mechanochemical reaction cycle. Crystal structures of myosin in different states have provided important structural insights into the myosin motor cycle when myosin is detached from F-actin. The difficulty of obtaining diffracting crystals, however, has prevented structure determination by crystallography of actomyosin complexes. Thus, although structural models exist of F-actin in complex with various myosins, a high-resolution structure of the F-actin–myosin complex is missing. Here, using electron cryomicroscopy, we present the structure of a human rigor actomyosin complex at an average resolution of 3.9 Å. The structure reveals details of the actomyosin interface, which is mainly stabilized by hydrophobic interactions. The negatively charged amino (N) terminus of actin interacts with a conserved basic motif in loop 2 of myosin, promoting cleft closure in myosin. Surprisingly, the overall structure of myosin is similar to rigor-like myosin structures in the absence of F-actin, indicating that F-actin binding induces only minimal conformational changes in myosin. A comparison with pre-powerstroke and intermediate (Pi-release) states of myosin allows us to discuss the general mechanism of myosin binding to F-actin. Our results serve as a strong foundation for the molecular understanding of cytoskeletal diseases, such as autosomal dominant hearing loss and diseases affecting skeletal and cardiac muscles, in particular nemaline myopathy and hypertrophic cardiomyopathy.
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The role of Ki-67 in mitotic cell division has been a mystery. Extensive imaging reveals that this highly positively charged protein coats chromosomes to prevent them from coalescing.
A study reveals that human-driven disturbances in previously undisturbed Amazon rainforest can cause biodiversity losses as severe as those of deforestation. Urgent policy interventions are needed to preserve forest quality.
The protein PKM-ζ has been proposed to regulate the maintenance of memory in rodents, but this theory has been questioned. The finding that another isoform of the protein acts as a backup if PKM-ζ is lacking will influence this debate.
At what times of year are phenological events across species sensitive to climatic variables, and how sensitive are they? Answers to these questions emerge from the analysis of a wealth of long-term data sets.
Differences in phenological responses to climate change among species can desynchronise ecological interactions and thereby threaten ecosystem function. To assess these threats, we must quantify the relative impact of climate change on species at different trophic levels. Here, we apply a Climate Sensitivity Profile approach to 10,003 terrestrial and aquatic phenological data sets, spatially matched to temperature and precipitation data, to quantify variation in climate sensitivity. The direction, magnitude and timing of climate sensitivity varied markedly among organisms within taxonomic and trophic groups. Despite this variability, we detected systematic variation in the direction and magnitude of phenological climate sensitivity. Secondary consumers showed consistently lower climate sensitivity than other groups. We used mid-century climate change projections to estimate that the timing of phenological events could change more for primary consumers than for species in other trophic levels (6.2 versus 2.5–2.9 days earlier on average), with substantial taxonomic variation (1.1–14.8 days earlier on average).
Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important part in innate immune responses. Viral-encoded core basic proteins compact viral genomes, but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones. Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles, it is unknown whether protein VII affects cellular chromatin. Here we show that protein VII alters cellular chromatin, leading us to hypothesize that this has an impact on antiviral responses during adenovirus infection in human cells. We find that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter the protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in the chromatin of members of the high-mobility-group protein B family (HMGB1, HMGB2 and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses. We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation-induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together, our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signalling.
Concerted political attention has focused on reducing deforestation, and this remains the cornerstone of most biodiversity conservation strategies. However, maintaining forest cover may not reduce anthropogenic forest disturbances, which are rarely considered in conservation programmes. These disturbances occur both within forests, including selective logging and wildfires, and at the landscape level, through edge, area and isolation effects. Until now, the combined effect of anthropogenic disturbance on the conservation value of remnant primary forests has remained unknown, making it impossible to assess the relative importance of forest disturbance and forest loss. Here we address these knowledge gaps using a large data set of plants, birds and dung beetles (1,538, 460 and 156 species, respectively) sampled in 36 catchments in the Brazilian state of Pará. Catchments retaining more than 69–80% forest cover lost more conservation value from disturbance than from forest loss. For example, a 20% loss of primary forest, the maximum level of deforestation allowed on Amazonian properties under Brazil’s Forest Code, resulted in a 39–54% loss of conservation value: 96–171% more than expected without considering disturbance effects. We extrapolated the disturbance-mediated loss of conservation value throughout Pará, which covers 25% of the Brazilian Amazon. Although disturbed forests retained considerable conservation value compared with deforested areas, the toll of disturbance outside Pará’s strictly protected areas is equivalent to the loss of 92,000–139,000 km2 of primary forest. Even this lowest estimate is greater than the area deforested across the entire Brazilian Amazon between 2006 and 2015 (ref. 10). Species distribution models showed that both landscape and within-forest disturbances contributed to biodiversity loss, with the greatest negative effects on species of high conservation and functional value. These results demonstrate an urgent need for policy interventions that go beyond the maintenance of forest cover to safeguard the hyper-diversity of tropical forest ecosystems.
The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway2,3. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy. Here we report the discovery of ahighly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.
Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis. This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes and the discovery of proteins at the chromosome surface, the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization.
The typically dark surface of the dwarf planet Ceres is punctuated by areas of much higher albedo, most prominently in the Occator crater. These small bright areas have been tentatively interpreted as containing a large amount of hydrated magnesium sulfate, in contrast to the average surface, which is a mixture of low-albedo materials and magnesium phyllosilicates, ammoniated phyllosilicates and carbonates. Here we report high spatial and spectral resolution near-infrared observations of the bright areas in the Occator crater on Ceres. Spectra of these bright areas are consistent with a large amount of sodium carbonate, constituting the most concentrated known extraterrestrial occurrence of carbonate on kilometre-wide scales in the Solar System. The carbonates are mixed with a dark component and small amounts of phyllosilicates, as well as ammonium carbonate or ammonium chloride. Some of these compounds have also been detected in the plume of Saturn’s sixth-largest moon Enceladus. The compounds are endogenous and we propose that they are the solid residue of crystallization of brines and entrained altered solids that reached the surface from below. The heat source may have been transient (triggered by impact heating). Alternatively, internal temperatures may be above the eutectic temperature of subsurface brines, in which case fluids may exist at depth on Ceres today.
G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, theβ2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity.
Three-dimensional graphene architectures with periodic nanopores—reminiscent of zeolite frameworks—are of topical interest because of the possibility of combining the characteristics of graphene with a three-dimensional porous structure. Lately, the synthesis of such carbons has been approached by using zeolites as templates and small hydrocarbon molecules that can enter the narrow pore apertures. However, pyrolytic carbonization of the hydrocarbons (a necessary step in generating pure carbon) requires high temperatures and results in non-selective carbon deposition outside the pores. Here, we demonstrate that lanthanum ions embedded in zeolite pores can lower the temperature required for the carbonization of ethylene or acetylene. In this way, a graphene-like carbon structure can be selectively formed inside the zeolite template, without carbon being deposited at the external surfaces. X-ray diffraction data from zeolite single crystals after carbonization indicate that electron densities corresponding to carbon atoms are generated along the walls of the zeolite pores. After the zeolite template is removed, the carbon framework exhibits an electrical conductivity that is two orders of magnitude higher than that of amorphous mesoporous carbon. Lanthanum catalysis allows a carbon framework to form in zeolite pores with diameters of less than 1 nanometre; as such, microporous carbon nanostructures can be reproduced with various topologies corresponding to different zeolite pore sizes and shapes. We demonstrate carbon synthesis for large-pore zeolites (FAU, EMT and beta), a one-dimensional medium-pore zeolite (LTL), and even small-pore zeolites (MFI and LTA). The catalytic effect is a common feature of lanthanum, yttrium and calcium, which are all carbide-forming metal elements. We also show that the synthesis can be readily scaled up, which will be important for practical applications such as the production of lithium-ion batteries and zeolite-like catalyst supports.
The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on. Replication–transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity. Collisions may also trigger mutations, which are major contributors to genetic disease and evolution. However, the nature andmechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication–transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encountersa transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major σ factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication–transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements.
Along ultraslow-spreading ridges, where oceanic tectonic plates drift very slowly apart, conductive cooling is thought to limit mantle melting and melt production has been inferred to be highly discontinuous. Along such spreading centres, long ridge sections without any igneous crust alternate with magmatic sections that host massive volcanoes capable of strong earthquakes. Hence melt supply, lithospheric composition and tectonic structure seem to vary considerably along the axis of the slowest-spreading ridges. However, owing to the lack of seismic data, the lithospheric structure of ultraslow ridges is poorly constrained. Here we describe the structure and accretion modes of two end-member types of oceanic lithosphere using a detailed seismicity survey along 390 kilometres of ultraslow-spreading ridge axis. We observe that amagmatic sections lack shallow seismicity in the upper 15 kilometres of the lithosphere, but unusually contain earthquakes down to depths of 35 kilometres. This observation implies a cold, thick lithosphere, with an upper aseismic zone that probably reflects substantial serpentinization. We find that regions of magmatic lithosphere thin dramatically under volcanic centres, and infer that the resulting topography of the lithosphere–asthenosphere boundary could allow along-axis melt flow, explaining the uneven crustal production at ultraslow-spreading ridges. The seismicity data indicate that alteration in ocean lithosphere may reach far deeper than previously thought, with important implications towards seafloor deformation and fluid circulation.
Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion. GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered. Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein–drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14 °C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs.
The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis. Small-molecule electrocatalysts for processes of this type are promising targets for further development, as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen. Complexes with tethered amines that resemble the active site of hydrogenases have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance. Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however. Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation. These catalysts exhibit good activity (1–2 turnovers per second) with a wide range of alcohols and have great promise for electro-organic synthesis. Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2′-bipyridine)Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2′-bipyridine)Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how electron-proton-transfer mediators, such as TEMPO, may be used in combination with first-row transition metals, such as copper, to achieve efficient two-electron electrochemical processes, thereby introducing a new concept for the development of non-precious-metal electrocatalysts.
Photoelectric heating—heating of dust grains by far-ultraviolet photons—has long been recognized as the primary source of heating for the neutral interstellar medium. Simulations of spiral galaxies have shown some indication that photoelectric heating could suppress star formation; however, simulations that includephotoelectric heating have typically shown that it has little effect on the rate of star formation in either spiral galaxies or dwarf galaxies, which suggests that supernovae are responsible for setting the gas depletion time in galaxies. This result is in contrast with recent work indicating that a star formation law that depends on galaxy metallicity—as is expected with photoelectric heating, but not with supernovae—reproduces the present-day galaxy population better than does a metallicity-independent one. Here we report a series of simulations of dwarf galaxies, the class of galaxy inwhich the effects of both photoelectric heating and supernovae are expected to be strongest. We simultaneously include space- and time-dependent photoelectric heating in our simulations, and we resolve the energy-conserving phase of every supernova blast wave, which allows us to directly measure the relative importance of feedback by supernovae and photoelectric heating in suppressing star formation. We find that supernovae are unable to account for the observed large gas depletion times in dwarf galaxies. Instead, photoelectric heating is the dominant means by which dwarf galaxies regulate their star formation rate at any given time, suppressing the rate by more than an order of magnitude relative to simulations with only supernovae.
A range of neuronal mechanisms can enable animals to detect the direction of visual motion. Computational models now indicate that a factor as simple as eye size might explain some of this diversity.
Directional selectivity in the detection of moving visual stimuli critically depends on starburst amacrine cells, which have been studied primarily in rabbit retina; a large-scale reconstruction of the mouse retina at a single-synapse level, along with experimental and theoretical analysis, shows that mouse retinal circuitry is adapted to the smaller eye size of mice.
This paper reports the identification of a new cereblon-modulating agent, CC-885, which targets the translation termination factor GSPT1 and demonstrates anti-tumour activity in patient-derived tumour cells; the crystal structure of the cereblon–DDB1–GSPT1–CC-885 complex reveals a common motif for cereblon-substrate recruitment.
Our current understanding of the curved space-time around supermassive black holes is based on actively accreting black holes, which make up only ten per cent or less of the overall population. X-ray observations of that small fraction reveal strong gravitational redshifts that indicate that many of these black holes are rapidly rotating; however, selection biases suggest that these results are not necessarily reflective of the majority of black holes in the Universe. Tidal disruption events, where a star orbiting an otherwise dormant black hole gets tidally shredded and accreted onto the black hole, can provide a short, unbiased glimpse at the space-time around the other ninety per cent of black holes. Observations of tidal disruptions have hitherto revealed the formation of an accretion disk and the onset of an accretion-powered jet, but have failed to reveal emission from the inner accretion flow, which enables the measurement of black hole spin. Here we report observations of reverberation arising from gravitationally redshifted iron Kα photons reflected off the inner accretion flow in the tidal disruption event Swift J1644+57. From the reverberation timescale, we estimate the mass of the black hole to be a few million solar masses, suggesting an accretion rate of 100 times the Eddington limit or more. The detection of reverberation from the relativistic depths of this rare super-Eddington event demonstrates that the X-rays do not arise from the relativistically moving regions of a jet, as previously thought.
Ongoing declines in the structure and function of the world’s coral reefs require novel approaches to sustain these ecosystems and the millions of people who depend on them. A presently unexplored approach that draws on theory and practice in human health and rural development is to systematically identify and learn from the ‘outliers’—places whereecosystems are substantially better (‘bright spots’) or worse (‘dark spots’) than expected, given the environmental conditions and socioeconomic drivers they are exposed to. Here we compile data from more than 2,500 reefs worldwide and develop a Bayesian hierarchical model to generate expectations of how standing stocks of reef fish biomass are related to 18 socioeconomic drivers and environmental conditions. We identify 15 bright spots and 35 dark spots among our global survey of coral reefs, defined as sites that have biomass levels more than two standard deviations from expectations. Importantly, bright spots are not simply comprised of remote areas with low fishing pressure; they include localities where human populations and use of ecosystem resources is high, potentially providing insights into how communities have successfully confronted strong drivers of change. Conversely, dark spots are not necessarily the sites with the lowest absolute biomass and even include some remote, uninhabited locations often considered near pristine. We surveyed local experts about social, institutional, and environmental conditions at these sites to reveal that bright spots are characterized by strong sociocultural institutions such as customary taboos and marine tenure, high levels of local engagement in management, high dependence on marine resources, and beneficial environmental conditions such as deep-water refuges. Alternatively, dark spots are characterized by intensive capture and storage technology and a recent history of environmental shocks. Our results suggest that investments in strengthening fisheries governance, particularly aspects such as participation and property rights, could facilitate innovative conservation actions that help communities defy expectations of global reef degradation.
The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport. There has been considerable interest in repurposing such structures for applications ranging from targeted delivery to multivalent immunogen presentation. The ability to design proteins that self-assemble into precisely specified, highly ordered icosahedral structures would open the door to a new generation of protein containers with properties custom-tailored to specific applications. Here we describe the computational design of a 25-nanometre icosahedral nanocage that self-assembles from trimeric protein building blocks. The designed protein was produced in Escherichia coli, and found by electron microscopy to assemble into a homogenous population of icosahedral particles nearly identical to the design model. The particles are stable in 6.7 molar guanidine hydrochloride at up to 80 degrees Celsius, and undergo extremely abrupt, but reversible, disassembly between 2 molar and 2.25 molar guanidinium thiocyanate. The icosahedron is robust to genetic fusions: one or two copies of green fluorescent protein (GFP) can be fused to each of the 60 subunits to create highly fluorescent‘standard candles’ for use in light microscopy, and a designed protein pentamer can be placed in the centre of each of the 20 pentameric faces to modulate the size of the entrance/exit channels of the cage. Such robust and customizable nanocages should have considerable utility in targeted drugdelivery, vaccine design and synthetic biology.
The theory of plate tectonics describes how the surface of Earth is split into an organized jigsaw of seven large plates of similar sizes and a population of smaller plates whose areas follow a fractal distribution. The reconstruction of global tectonics during the past 200 million years suggests that this layout is probably a long-term feature of Earth, but the forces governing it are unknown. Previous studies, primarily based on the statistical properties of plate distributions, were unable to resolve how the size of the plates is determined by the properties of the lithosphere and the underlying mantle convection. Here we demonstrate that the plate layout of Earth is produced by a dynamic feedback between mantle convection and the strength of the lithosphere. Using three-dimensional spherical models of mantle convection that self-consistently produce the plate size–frequency distribution observed for Earth, we show that subduction geometry drives the tectonic fragmentation that generates plates. The spacing between the slabs controls the layout of large plates, and the stresses caused by the bending of trenches break plates into smaller fragments. Our results explain why the fast evolution in small back-arc plates reflects the marked changes in plate motions during times of major reorganizations. Our study opens the way to using convection simulations with plate-like behaviour to unravel how global tectonics and mantle convection are dynamically connected.
Photon emitters placed in an optical cavity experience an environment that changes how they are coupled to the surrounding light field. In the weak-coupling regime, the extraction of light from the emitter is enhanced. But more profound effects emerge when single-emitter strong coupling occurs: mixed states are produced that are part light, part matter, forming building blocks for quantum information systems and for ultralow-power switches and lasers. Such cavity quantum electrodynamics has until now been the preserve of low temperatures and complicated fabrication methods, compromising its use. Here, by scaling the cavity volume to less than 40 cubic nanometres and using host–guest chemistry to align one to ten protectively isolated methylene-blue molecules, we reach the strong-coupling regime at room temperature and in ambient conditions. Dispersion curves from more than 50 such plasmonic nanocavities display characteristic light–matter mixing, with Rabi frequencies of 300 millielectronvolts for ten methylene-blue molecules, decreasing to 90 millielectronvolts for single molecules—matching quantitative models. Statistical analysis of vibrational spectroscopy time series and dark-field scattering spectra provides evidence of single-molecule strong coupling.This dressing of molecules with light can modify photochemistry, opening up the exploration of complex natural processes such as photosynthesis and the possibility of manipulating chemical bonds.
The N-terminal domains of gasdermin proteins cause pyroptotic cell death by oligomerizing to form membrane pores.
Deadly coral snakes warn predators through striking red-black banding. New data confirm that many harmless snakes have evolved to resemble coral snakes, and suggest that the evolution of this Batesian mimicry is not always a one-way street.
The early stages of human development are normally hidden within the womb, but improved techniques for culturing embryos from the blastocyst stage promise to make these steps easier to investigate.