The next president of the European Research Council will face the dual challenge of preserving the agency’s reputation for excellence while trying to address funding inequalities.
Sexual harassment is a stain on science — and we must all take a stand against it.
Chemists present a way to infer the enigmatic temperature variations inside a reactor.
Bid to use common anaesthetic for executions threatens to cut off supply to US hospitals.
South American SciELO project weighs up future after 15 years of free publishing.
Researchers fear that continuing budget fights will further harm government-funded science.
Campaigners want subsidies to be focused on conservation.
An influential US experiment prepares to release its first results.
Researchers will fly jet towards giant artificial particle cloud to test safety device.
Even one of the best known dinosaurs has kept some secrets. Here is what palaeontologists most want to know about the Famous tyrant.
By scanning blobs of brain activity, scientists may be able to decode people's thoughts, their dreams and even their intentions.
News & Views
A complete hominin cranium found at the archaeological site of Dmanisi shows remarkably primitive morphology, prompting its discoverers to propose that early forms of the genus Homo evolved as a single, highly variable lineage.
A detailed astrophysical model has been laid out that not only reproduces the far-infrared–radio correlation for galaxies that are actively forming stars, but also predicts how the correlation is modified at high redshift.
Two related nuclear receptors mediate circadian fat metabolism in two different tissues using a lipid messenger as an intermediary. This signalling pathway might be relevant to the understanding of metabolic disorders. See Letter p.550
The discovery of a new way of controlling a class of complex-oxide materials, known as the Ruddlesden–Popper series of structures, may lead the way to making electronically tunable microwave devices. See Letter p.532
Sophisticated microscopy analysis of conodont elements suggests that these mysterious fossil structures are not, as has been previously suggested, evolutionary precursors to vertebrate teeth. See Letter p.546
Carbon monoxide molecules are typically coupled together using metal catalysts. The discovery that boron, a non-metal, mediates such a reaction is startling, and raises the prospect of potentially useful carbon–carbon bond-forming processes.
Spectroscopic measurements of 43 candidates for distant galaxies have confirmed one to be the most remote galaxy securely identified to date — and it forms stars more than 100 times faster than the Milky Way. See Letter p.524
Of several dozen galaxies observed spectroscopically that are candidates for having a redshift (z) in excess of seven, only five have had their redshifts confirmed via Lyman α emission, at z = 7.008, 7.045, 7.109, 7.213 and 7.215 (refs 1, 2, 3, 4). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z > 6.5, given that Lyman α is resonantly scattered by neutral gas. The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman α difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman α emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy’s colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size, suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.
The physics of the superconducting state in two-dimensional (2D) electron systems is relevant to understanding the high-transition-temperature copper oxide superconductors and for the development of future superconductors based on interface electron systems. But it is not yet understood how fundamental superconducting parameters, such as the spectral density of states, change when these superconducting electron systems are depleted of charge carriers. Here we use tunnel spectroscopy with planar junctions to measure the behaviour of the electronic spectral density of states as a function of carrier density, clarifying this issue experimentally. We chose the conducting LaAlO3–SrTiO3 interface as the 2D superconductor, because this electron system can be tuned continuously with an electric gate field. We observed an energy gap of the order of 40 microelectronvolts in the density of states, whose shape is well described by the Bardeen–Cooper–Schrieffer superconducting gap function. In contrast to the dome-shaped dependence of the critical temperature, the gap increases with charge carrier depletion in both the underdoped region and the overdoped region. These results are analogous to the pseudogap behaviour of the high-transition-temperature copper oxide superconductors and imply that the smooth continuation of the superconducting gap into pseudogap-like behaviour could be a general property of 2D superconductivity.
The miniaturization and integration of frequency-agile microwave circuits—relevant to electronically tunable filters, antennas, resonators and phase shifters—with microelectronics offers tantalizing device possibilities, yet requires thin films whose dielectric constant at gigahertz frequencies can be tuned by applying a quasi-static electric field. Appropriate systems such as BaxSr1−xTiO3 have a paraelectric–ferroelectric transition just below ambient temperature, providing high tunability. Unfortunately, such films suffer significant losses arising from defects. Recognizing that progress is stymied by dielectric loss, we start with a system with exceptionally low loss—Srn+1TinO3n+1 phases—in which (SrO)2 crystallographic shear planes provide an alternative to the formation of point defects for accommodating non-stoichiometry. Here we report the experimental realization of a highly tunable ground state arising from the emergence of a local ferroelectric instability in biaxially strained Srn+1TinO3n+1 phases with n ≥ 3 at frequencies up to 125 GHz. In contrast to traditional methods of modifying ferroelectrics—doping or strain—in this unique system an increase in the separation between the (SrO)2 planes, which can be achieved by changing n, bolsters the local ferroelectric instability. This new control parameter, n, can be exploited to achieve a figure of merit at room temperature that rivals all known tunable microwave dielectrics.
More than 85 per cent of all chemical industry products are made using catalysts, the overwhelming majority of which are heterogeneous catalysts that function at the gas–solid interface. Consequently, much effort is invested in optimizing the design of catalytic reactors, usually by modelling the coupling between heat transfer, fluid dynamics and surface reaction kinetics. The complexity involved requires a calibration of model approximations against experimental observations, with temperature maps being particularly valuable because temperature control is often essential for optimal operation and because temperature gradients contain information about the energetics of a reaction. However, it is challenging to probe the behaviour of a gas inside a reactor without disturbing its flow, particularly when trying also to map the physical parameters and gradients that dictate heat and mass flow and catalytic efficiency. Although optical techniques and sensors have been used for that purpose, the former perform poorly in opaque media and the latter perturb the flow. NMR thermometry can measure temperature non-invasively, but traditional approaches applied to gases produce signals that depend only weakly on temperature are rapidly attenuated by diffusion or require contrast agents that may interfere with reactions. Here we present a new NMR thermometry technique that circumvents these problems by exploiting the inverse relationship between NMR linewidths and temperature caused by motional averaging in a weak magnetic field gradient. We demonstrate the concept by non-invasively mapping gas temperatures during the hydrogenation of propylene in reactors packed with metal nanoparticles and metal–organic framework catalysts, with measurement errors of less than four per cent of the absolute temperature. These results establish our technique as a non-invasive tool for locating hot and cold spots in catalyst-packed gas–solid reactors, with unprecedented capabilities for testing the approximations used in reactor modelling.
The El Niño–Southern Oscillation (ENSO) drives substantial variability in rainfall, severe weather, agricultural production, ecosystems and disease in many parts of the world. Given that further human-forced changes in the Earth’s climate system seem inevitable, the possibility exists that the character of ENSO and its impacts might change over the coming century. Although this issue has been investigated many times during the past 20 years, there is very little consensus on future changes in ENSO, apart from an expectation that ENSO will continue to be a dominant source of year-to-year variability. Here we show that there are in fact robust projected changes in the spatial patterns of year-to-year ENSO-driven variability in both surface temperature and precipitation. These changes are evident in the two most recent generations of climate models, using four different scenarios for CO2 and other radiatively active gases. By the mid- to late twenty-first century, the projections include an intensification of both El-Niño-driven drying in the western Pacific Ocean and rainfall increases in the central and eastern equatorial Pacific. Experiments with an Atmospheric General Circulation Model reveal that robust projected changes in precipitation anomalies during El Niño years are primarily determined by a nonlinear response to surface global warming. Uncertain projected changes in the amplitude of ENSO-driven surface temperature variability have only a secondary role. Projected changes in key characteristics of ENSO are consequently much clearer than previously realized.
Conodonts are an extinct group of jawless vertebrates whose tooth-like elements are the earliest instance of a mineralized skeleton in the vertebrate lineage, inspiring the ‘inside-out’ hypothesis that teeth evolved independently of the vertebrate dermal skeleton and before the origin of jaws. However, these propositions have been based on evidence from derived euconodonts. Here we test hypotheses of a paraconodont ancestry of euconodonts using synchrotron radiation X-ray tomographic microscopy to characterize and compare the microstructure of morphologically similar euconodont and paraconodont elements. Paraconodonts exhibit a range of grades of structural differentiation, including tissues and a pattern of growth common to euconodont basal bodies. The different grades of structural differentiation exhibited by paraconodonts demonstrate the stepwise acquisition of euconodont characters, resolving debate over the relationship between these two groups. By implication, the putative homology of euconodont crown tissue and vertebrate enamel must be rejected as these tissues have evolved independently and convergently. Thus, the precise ontogenetic, structural and topological similarities between conodont elements and vertebrate odontodes appear to be a remarkable instance of convergence. The last common ancestor of conodonts and jawed vertebrates probably lacked mineralized skeletal tissues. The hypothesis that teeth evolved before jaws and the inside-out hypothesis of dental evolution must be rejected; teeth seem to have evolved through the extension of odontogenic competence from the external dermis to internal epithelium soon after the origin of jaws.
Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or use. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding and is repressed by Rev-erbα/β and an HDAC3-containing complex during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes, suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPARδ-dependent de novo lipogenic pathway in the liver that modulates fat use by muscle via a circulating lipid. The nuclear receptor PPARδ controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPARδ activation increases, whereas hepatocyte-Ppard deletion reduces, muscle fatty acid uptake. Unbiased metabolite profiling identifies phosphatidylcholine 18:0/18:1 (PC(18:0/18:1) as a serum lipid regulated by diurnal hepatic PPARδ activity. PC(18:0/18:1) reduces postprandial lipid levels and increases fatty acid use through muscle PPARα. High-fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice (also known as Lepr−/−) improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy use in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPARδ–PC(18:0/18:1) signalling in metabolic disorders, including obesity.
Shoot growth depends on meristems, pools of stem cells that are maintained by a negative feedback loop between the CLAVATA pathway and the WUSCHEL homeobox gene. CLAVATA signalling involves a secreted peptide, CLAVATA3 (CLV3), and its perception by cell surface leucine-rich repeat (LRR) receptors, including the CLV1 receptor kinase and a LRR receptor-like protein, CLV2 (ref. 4). However, the signalling mechanisms downstream of these receptors are poorly understood, especially for LRR receptor-like proteins, which lack a signalling domain. Here we show that maize COMPACT PLANT2 (CT2) encodes the predicted α-subunit (Gα) of a heterotrimeric GTP binding protein. Maize ct2 phenotypes resemble Arabidopsis thaliana clavata mutants, and genetic, biochemical and functional assays indicate that CT2/Gα transmits a stem-cell-restrictive signal from a CLAVATA LRR receptor, suggesting a new function for Gα signalling in plants. Heterotrimeric GTP-binding proteins are membrane-associated molecular switches that are commonly activated by ligand binding to an associated seven-pass transmembrane (7TM) G-protein-coupled receptor (GPCR). Recent studies have questioned the idea that plant heterotrimeric G proteins interact with canonical GPCRs, and our findings suggest that single pass transmembrane receptors act as GPCRs in plants, challenging the dogma that GPCRs are exclusively 7TM proteins.
Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1), these include widely expressed restriction factors, such as APOBEC3 proteins, TRIM5-α, BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN). Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like, IFN-induced myxovirus resistance 2 (MX2, also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-α-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested, has equivalent or reduced effects on divergent simian immunodeficiency viruses, and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late post-entry step, with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally, human MX1 (also known as MXA), a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus, does not affect HIV-1, whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.
HIV-1 replication can be inhibited by type I interferon (IFN), and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN. However, none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle in human cells. Here, by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-α at early steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-α. HIV-1 reverse transcription proceeds normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected, to alter the nuclear import pathways used by HIV-1 confer resistance to MX2, whereas preventing cell division increases MX2 potency. Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.
G-protein-coupled receptors (GPCRs) are integral membrane proteins that have an essential role in human physiology, yet the molecular processes through which they bind to their endogenous agonists and activate effector proteins remain poorly understood. So far, it has not been possible to capture an active-state GPCR bound to its native neurotransmitter. Crystal structures of agonist-bound GPCRs have relied on the use of either exceptionally high-affinity agonists or receptor stabilization by mutagenesis. Many natural agonists such as adrenaline, which activates the β2-adrenoceptor (β2AR), bind with relatively low affinity, and they are often chemically unstable. Using directed evolution, we engineered a high-affinity camelid antibody fragment that stabilizes the active state of the β2AR, and used this to obtain crystal structures of the activated receptor bound to multiple ligands. Here we present structures of the active-state human β2AR bound to three chemically distinct agonists: the ultrahigh-affinity agonist BI167107, the high-affinity catecholamine agonist hydroxybenzyl isoproterenol, and the low-affinity endogenous agonist adrenaline. The crystal structures reveal a highly conserved overall ligand recognition and activation mode despite diverse ligand chemical structures and affinities that range from 100 nM to ∼80 pM. Overall, the adrenaline-bound receptor structure is similar to the others, but it has substantial rearrangements in extracellular loop three and the extracellular tip of transmembrane helix 6. These structures also reveal a water-mediated hydrogen bond between two conserved tyrosines, which appears to stabilize the active state of the β2AR and related GPCRs.