Research articles

The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.

A new approach to accurately determine mutation frequencies with RNA virus populations called circular sequencing (CirSeq) has been developed; a study of the genetic composition of populations of poliovirus shows the fitness landscape for each nucleotide variant in an evolving RNA virus.

Oncogenic Nras in mouse haematopoietic stem cells can increase the probability of cell division in some cells and decrease it in others; this bimodal activity explains how this single pre-leukaemic mutation can increase proliferation without reducing competitiveness by clonally expanding the rapidly dividing cell population and also promoting long-term self-renewal of stem cells.

The mRNAs of higher eukaryotes are extensively modified internally with N⁶-methyladenosine, but the specific functional role of this modification has been unclear; here this modification on mRNA is shown to be recognized by several proteins, the modification and its recognition serve to regulate the RNA’s lifetime.

Engineered dissipation is used to deterministically produce and stabilize entanglement between two trapped-ion quantum bits, independently of their initial states; the entanglement is stabilized even in the presence of experimental noise and decoherence.

Femtosecond crystallography with an X-ray free-electron laser is used to analyse micrometre-sized protein crystals, generating a high-resolution structure of the protein without previous knowledge of what it looks like.

X-ray crystal structures of a voltage-gated Na⁺channel mutated to be highly Ca²⁺selective provide a framework for understanding the mechanisms of ion selectivity and conductance in vertebrate voltage-gated Ca²⁺channels.

Mitophagy is the elimination of damaged mitochondria by the autophagosome regulated by the ubiquitin ligase, parkin and the kinase PINK1; a genome-wide RNAi screen with high-content microscopy has identified new genes that have an upstream role in parkin translocation to the mitochondria.

RNA adopts vast and complicated secondary structures in the living cell; reported here is a new approach, structure-seq, that characterises RNA structure in vivo on a genome-wide scale at nucleotide resolution and should be applicable to any organism.

An entangled Bell state of two superconducting quantum bits can be stabilized for an arbitrary time using an autonomous feedback scheme, that is, one that does not require a complicated external error-correcting feedback loop.

A comprehensive study into the effects of polymorphisms on gene expression dynamics during a 12-hour development period of Caenorhabditis elegans shows that both cis and trans expression quantitative trait loci (eQTLs) can increase and decrease gene expression, depending on the time point, and that trans eQTLs can act as modifiers of expression during a given period of development.

This study describes comprehensive synaptic engulfment by astrocytes, mediating synapse elimination in an activity-dependent manner; this elimination process involves the MEGF10 and MERTK phagocytic pathways and persists into adulthood, with mutant mice that lack these pathways in astrocytes exhibiting a failure to refine retinogeniculate connections during development.

Chemical analysis of the meteorite NWA 7533 indicates that it may be a Martian regolith breccia and, if so, that the crust of Mars may have formed in the first 100 million years of the planet’s history.

Plant invasions are thought to alter the ecosystem in a way that disadvantages the native species, making re-establishment after eradication difficult; here, on returning to a site at which an invasive plant altered nitrogen-mineralization levels several decades ago, mineralization is found to have returned to pre-invasion levels, although these new conditions favour new invaders over the natives.

Draft genomes of two south-central Siberian individuals dating to 24,000 and 17,000 years ago show that they are genetically closely related to modern-day western Eurasians and Native Americans but not to east Asians; the results have implications for our understanding of the origins of Native Americans.

There are many uses for surfaces that can stay dry, self-clean or resist icing, and many applications benefit from minimizing the contact time between a surface and any drops that may come into contact with it; drops are now shown to bounce off faster when using a superhydrophobic surface with a morphology that redistributes the liquid mass so that the centre of the drop assists in the recoil.

Divergent angiocrine signals from liver sinusoidal endothelial cells elicit regeneration after immediate injury and provoke fibrosis after chronic insult.

An analysis of regional variations in global inland water surface area, dissolved CO₂ and gas transfer velocity yields a global CO₂ evasion rate of 2.1 × 10¹⁵ grams of carbon per year, which is higher than previous estimates owing to a larger contribution from streams and rivers.