The first outbreak of yellow fever in Angola in almost 30 years illustrates the danger of a short attention span when confronting epidemic threats.
To boost nuclear security, research reactors must eliminate highly enriched uranium.
Mental illness is moving up the global agenda — but there is still much to do.
Rhetoric in US presidential campaign concerns researchers — particularly Muslims.
Multiple teams finally have the material they need to repeat enigmatic experiment.
Fetal tissue may prove crucial to probing link between virus and birth defects.
Airborne experiments aim to fill in the blanks of global water resources as the climate changes.
Human Brain Project asks wider neuroscience community to start using its hardware and software.
Nations debate how to protect biodiversity in the high seas.
Smartphone apps claim to help conditions from addiction to schizophrenia, but few have been thoroughly tested.
News & Views
Detailed measurements of radioisotopes in deep-sea deposits, plus modelling of how they reached Earth, indicate that many supernovae have occurred near enough to have potentially influenced evolution. See Letters p.69 & p.73
A protein fragment released by filaments of the fungus Candida albicans destroys host cells. This is the first demonstration that human fungal pathogens other than moulds can release toxic peptides. See Article p.64
An analysis of changes in island topography and climate that have occurred since the last glacial maximum 21,000 years ago shows how sea-level change has influenced the current biodiversity of oceanic islands. See Letter p.99
A reconstruction of 1,200 years of water's history in the Northern Hemisphere, based on proxy data, fuels the debate about whether anthropogenic climate change affected twentieth-century precipitation. See Letter p.94
A clever dissection of the roles of the Ptchd1 gene in the brains of mice demonstrates one way to untangle the complex relationships between the causes and symptoms of neurodevelopmental disorders. See Article p.58
A high-throughput approach has found clusters of DNA double-strand breaks in neural cells. Most of the clusters are in large genes that are associated with neural function, which suggests that the breaks may have tissue-specific roles.
The potential of soils to mitigate greenhouse gas emissions has not been exploited; here we discuss and recommend research and technology developments to implement mitigation practices.
PTCHD1 deletion in humans leads to attention deficits, intellectual disability, and autism spectrum disorders; mouse PTCHD1 is enriched in the thalamic reticular nucleus (TRN) and TRN-restricted Ptchd1 deletion in mice led to attention-deficit hyperactivity, which could be rescued by modulating calcium-dependent potassium channel activity, suggesting that a TRN deficit may underlie core impairments associated with neurodevelopmental disorders and it may be possible to identify therapeutic targets for individuals with attention disorders.
This study identifies a cytolytic peptide toxin in the opportunistic human fungal pathogen Candida albicans—the peptide is both a crucial virulence factor that permeabilizes the host cell plasma membrane and a key signal that triggers a host danger response pathway.
The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2–4 million years, based on the total rate in the Milky Way (2.0 ± 0.7 per century). Recent massive-star and supernova activity in Earth’s vicinity may be traced by radionuclides with half-lives of up to 100 million years, if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is 60Fe (with a half-life of 2.6 million years), which is ejected in supernova explosions and winds from massive stars. Here we report that the 60Fe signal observed previously in deep-sea crusts is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for 60Fe deposition via the accretion of interstellar dust particles. Our results reveal 60Fe interstellar influxes onto Earth at 1.5–3.2 million years ago and at 6.5–8.7 million years ago. The signal measured implies that a few per cent of fresh 60Fe was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.
The signature of 60Fe in deep-sea crusts indicates that one or more supernovae exploded in the solar neighbourhood about 2.2 million years ago. Recent isotopic analysis is consistent with a core-collapse or electron-capture supernova that occurred 60 to 130 parsecs from the Sun. Moreover, peculiarities in the cosmic ray spectrum point to a nearby supernova about two million years ago. The Local Bubble of hot, diffuse plasma, in which the Solar System is embedded, originated from 14 to 20 supernovae within a moving group, whose surviving members are now in the Scorpius–Centaurus stellar association. Here we report calculations of the most probable trajectories and masses of the supernova progenitors, and hence their explosion times and sites. The 60Fe signal arises from two supernovae at distances between 90 and 100 parsecs. The closest occurred 2.3 million years ago at present-day galactic coordinates l = 327°, b = 11°, and the second-closest exploded about 1.5 million years ago at l = 343°, b = 25°, with masses of 9.2 and 8.8 times the solar mass, respectively. The remaining supernovae, which formed the Local Bubble, contribute to a smaller extent because they happened at larger distances and longer ago (60Fe has a half-life of 2.6 million years). There are uncertainties relating to the nucleosynthesis yields and the loss of 60Fe during transport, but they do not influence the relative distribution of 60Fe in the crust layers, and therefore our model reproduces the measured relative abundances very well.
A feedback-control algorithm implemented using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond is demonstrated; the algorithm uses coherent feedback to overcome the limitations of measurement-based feedback and protects the qubit against intrinsic dephasing noise, making it stable for milliseconds.
Ab initio calculations are used to determine the contribution of quantum fluctuations to the crystal structure of the high-pressure superconducting phase of H3S and D3S; the quantum nature of the proton is found to fundamentally change the superconducting phase diagram of H3S.
Insects are captured by the carnivorous plant Nepenthes alata when they ‘aquaplane’ on the wet rim, or ‘peristome’, of the plant’s pitcher organ; here it is shown that unidirectional water flow is crucial to the complete wetting of the peristome, and that the underlying mechanism involves multiscale structural features.
Enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene is demonstrated using a two-phase terpene synthesis strategy.
A very large set of proxy data is used to reconstruct Northern Hemisphere hydroclimate variability over the past twelve centuries, to benchmark climate model simulations of hydroclimate; the twentieth-century intensification of hydroclimate extremes seen in the model simulations is not supported by the proxy reconstruction.
Changes in island area, isolation and connectivity observed since the Last Glacial Maximum have had measurable effects on present-day biodiversity, with formerly larger and less well connected islands having a greater number of endemic species.
Exposure to predator scents triggers an instinctive fear response in mice, including a surge in blood levels of stress hormones; here, the amygdalo-piriform transition area is identified as provoking these hormonal responses.
Haploid human embryonic stem cells have been derived from haploid oocytes, the cells maintain a normal haploid karyotype as pluripotent cells and, unexpectedly, as differentiated cells — loss-of-function genetic screens previously performed with haploid embryonic stem cells in mice can now be performed in humans.
Uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue is supported by a burst of mitochondrial reactive oxygen species upon cold exposure.
Lypd8 protein derived from intestinal epithelial cells binds to flagellated bacteria to reduce their motility, which limits the entry of Gram-negative bacteria into the inner colonic mucus and prevents invasion of colonic epithelia.
Gain of MEKK3 signalling is shown to cause cerebral cavernous malformations (CCMs) via activation of the target genes Klf2 and Klf4; endothelial-specific loss of MEKK3, KLF2 or KLF4 prevents lesion formation and lethality in a mouse CCM model.
Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies. IMiDs bind CRBN, the substrate receptor of the CUL4–RBX1–DDB1–CRBN (also known as CRL4CRBN) E3 ubiquitin ligase, and inhibit ubiquitination of endogenous CRL4CRBN substrates. Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3), and casein kinase 1α (CK1α), which contributes to its clinical efficacy in the treatment of multiple myeloma and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS), respectively. How lenalidomide alters the specificity of the ligase to degrade these proteins remains elusive. Here we present the 2.45 Å crystal structure of DDB1–CRBN bound to lenalidomide and CK1α. CRBN and lenalidomide jointly provide the binding interface for a CK1α β-hairpin-loop located in the kinase N-lobe. We show that CK1α binding to CRL4CRBN is strictly dependent on the presence of an IMiD. Binding of IKZF1 to CRBN similarly requires the compound and both, IKZF1 and CK1α, use a related binding mode. Our study provides a mechanistic explanation for the selective efficacy of lenalidomide in del(5q) MDS therapy. We anticipate that high-affinity protein–protein interactions induced by small molecules will provide opportunities for drug development, particularly for targeted protein degradation.
The crystal structures of the protease domain of separase are reported, showing how separase recognizes cohesin, and how phosphorylation of the cleavage site enhances separase activity.