Analysis highlights the risk faced by a newly distinct species.
The US government should not focus funds on the Zika virus at the expense of other health priorities.
In a region known to be seismically active, destruction on this scale was still a surprise.
Materials research is at the heart of efforts to keep the world’s reactors running well past 2050.
Digital scans will help researchers test whether she fell out of a tree.
Evolution of mathematics traced using unusually comprehensive genealogy database.
Modern archiving technology cannot keep up with the growing tsunami of bits. But nature may hold an answer to that problem already.
Snakes kill tens of thousands of people each year. But experts can't agree on how best to overcome a desperate shortage of antivenom.
News & Views
An antibody therapy markedly reduces aggregates of amyloid-β, the hallmark protein of Alzheimer's disease, and might slow cognitive decline in patients. Confirmation of a cognitive benefit would be a game-changer. See Article p.50
The Rosetta spacecraft made history by successfully orbiting a comet. Data from the craft now reveal the structure of the comet's dust particles, shedding light on the processes that form planetary systems. See Letter p.73
Production of the cell's translational apparatus, the ribosome, requires the orchestrated function of hundreds of proteins. A structure of its earliest precursor yields unprecedented insight into ribosome formation.
The Southern Ocean has become less salty during the past few decades. An analysis of sea-ice transport in the ocean suggests that this phenomenon can be explained by coupled changes in sea-ice drift and thickness. See Letter p.89
If a tumour outgrows its blood supply, oxygen levels in its cells decrease. It emerges that this change can alter gene expression by limiting the activity of TET enzymes, which remove methyl groups from DNA. See Article p.63
When and by which paths did early humans migrate into America? An analysis of ancient plant and animal remains revises the timeframe during which a route may have opened between ice sheets in northwest America. See Article p.45
During much of the last ice age, continental ice sheets prevented humans from migrating into North America from Siberia; an environmental reconstruction of the corridor that opened up between the Cordilleran and Laurentide ice sheets reveals that it would have been inhospitable to the initial colonizing humans, who therefore probably entered North America by a different route.
Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose-dependent slowing of clinical decline in treated patients.
Using a single-cell sequencing analysis in monkey embryos, and comparing the genes expressed during early development in this species with those in mice and in human pluripotent stem cells, the authors define characteristics of pluripotency ontogeny across mammalian species.
Hypoxia in solid tumours reduces the expression of tumour suppressor genes through an epigenetic mechanism.
Recently, temperate Earth-sized planets were discovered around the nearby star TRAPPIST-1; now, preliminary transmission spectra observations of the two inner planets by the Hubble Space Telescope suggest that these planets do not have a hydrogen-dominated atmosphere and are thus terrestrial, their atmospheric type still to be determined.
In situ measurements of dust particles at comet 67P/Churyumov–Gerasimenko confirm that the particles are aggregates of smaller, elongated grains even at the smallest sizes examined.
A two-mode waveguide is designed to realize a dynamical encircling of an exceptional point at which two resonances coincide in their frequency and their rate of decay; as a result the waveguide transmits only into a unique mode at either one of its two output ports.
The transfer of energy between two vibrational modes of an optomechanical device is achieved using topological operations; the key to this transfer is the existence of an exceptional point in the complex spectrum of the device.
Ablation cooling is demonstrated as an effective means of removing material using successive bursts of laser pulses with short intraburst delay times; the technique allows the overall pulse energy to be decreased, overcoming negative thermal effects during the ablation process.
Multiple lines of evidence indicate that the northward transport of sea ice from Antarctica can explain the bulk of the observed freshening in the Southern Ocean.
Analysis of multi-year nutrient enrichment experiments carried out on 45 global grassland sites show that an addition of an increasing number of nutrients leads to a reduction in plant species diversity, and competition for multiple below-ground resources promotes plant species diversity.
A brain circuit is identified through which serotonin induces an anxiety-like state; this circuit also mediates the anxiety-like behaviour induced by acute administration of the selective serotonin reuptake inhibitor fluoxetine and may underlie the early adverse events that some patients with anxiety disorders have to these types of drugs.
Patient-derived circulating tumour cells are used to characterize the dynamics and underlying plasticity of HER2 expression in non-HER2-amplified breast tumours.
A new endosomal tethering mechanism involving a mechanochemical cycle of the dimeric coiled-coil protein EEA1 regulated by Rab5:GTP binding and GTP hydrolysis.
A class of small molecules that stabilize a previously unrecognized inactive state of KSR is reported; the agonists synergize with MEK inhibitors to prevent growth of Ras mutant cell lines.
Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca2+ (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.