Research articles

In mice, chronic stimulation by repetitive sounds, whisker deflection, motor activity or seizures during a postnatal developmental critical period, leads to permanent reductions in brain microvascular density, an effect that impairs oxygen delivery to neurons but can be prevented by blocking nitric oxide signalling.

HMGA2 promotes lung cancer progression in mice and humans; in mouse and human lung cancer cells, HMGA2 competes with mRNAs like TGFBR3 for the let-7 microRNA family, and in human non-small-cell lung cancer tissue, expression levels of HMGA2 and TGFBR3 are correlated, suggesting that HMGA2 functions both as a protein-coding gene and as a non-coding RNA.

Using a peptide toxin and small vanilloid agonists as pharmacological probes, high-resolution electron cryo-microscopy structures of rat TRPV1–ligand complexes are solved; these structures highlight conformational differences between TRP and voltage-gated ion channels in their active states, and suggest a dual gating mechanism that may account for the ability of members of the TRP channel superfamily to integrate diverse physiological signals.

Crystallographic structural analysis of bound states of the GBR1 and GBR2 subunits of human GABA_B receptor shows that both subunits adopt an open conformation at rest — represented by the apo and antagonist-bound structures — and that only GBR1 closes in the activated state — represented by the agonist-bound structure.

A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized.

A mathematical modelling study assesses the role of peer behaviour and ‘herding’ behaviour in aggregating information through the peer-review process; peer review works best when reviewers exercise intermediate levels of subjectivity.

A full mitochondrial genome from a 400,000-year-old Middle Pleistocene hominin from Spain unexpectedly reveals a close relationship to Denisovans, a sister group to the Neanderthals, raising interesting questions about the origins of Neanderthals and Denisovans.

In a mouse model of pancreatic tumours driven by Kras mutations, the outcome of suppressing autophagy is shown to depend on the status of p53: if p53 is intact, deletion of key autophagy genes blocks the progression of pre-cancerous lesions to aggressive carcinomas; however, in the absence of p53, loss of autophagy accelerates tumorigenesis, accompanied by deregulation of cancer cell metabolism.

Cycles of electron capture and β⁻ decay involving neutron-rich nuclei at a typical depth of about 150 metres are found to cool the outer crust of a neutron star by emitting neutrinos while also thermally decoupling the surface layers from the deeper crust; this mechanism has been studied in other astrophysical environments, but has not hitherto been considered in neutron stars.

Saccharomyces cerevisiae bearing engineered alginate and mannitol catabolic pathways can ferment sugars from brown macroalgae to produce ethanol, potentially allowing the use of brown macroalgae as a viable feedstock for the production of biofuels and renewable chemicals.

This study establishes an important role for the enzyme Tet1 in erasing genomic imprinting in vivo — mice with a knockout of paternal Tet1 give rise to progeny with imprinting defects and associated growth and development defects, which leads to early embryonic lethality; furthermore, analysis of the DNA methylation dynamics in reprogramming primordial germ cells (PGCs) suggests that Tet1 is required at a late stage of the reprogramming process, in the second wave of DNA demethylation in PGCs.

The crystal structure of an archaeal Rce1 protein has been determined; this protein represents a novel type of intramembrane protease, with a distinct architecture and catalytic site.

Drilling by the Integrated Ocean Drilling Program has recovered primitive, modally layered, orthopyroxene-bearing cumulate rocks from the lower plutonic crust formed at a fast-spreading ridge, leading to a better-constrained estimate of the bulk composition of fast-spreading oceanic crust.

Many DNA processes require chromosomes to be held together by a ring-shaped complex called cohesin, but despite the importance of this protein, its interaction with DNA has not been reproduced in vitro; here, using purified yeast proteins, cohesin loading is successfully recapitulated, offering mechanistic insight into how the loader complex mediates topological cohesin binding.

Very slow cooling, over several days, of solutions of complementary-DNA-modified nanoparticles through the melting temperature of the system produces nanoparticle assemblies with the Wulff equilibrium crystal structure, thus showing that DNA hybridization can direct nanoparticle assembly along a pathway that mimics atomic crystallization.

The specificity of interferon effectors across an expanded range of viruses is studied, with results indicating that positive-sense single-stranded RNA viruses are more susceptible to interferon-stimulated gene activity than negative-sense RNA or DNA viruses; in addition, the DNA sensor cGAS is shown to have an unappreciated role in RNA virus inhibition.

This Analysis compares two large-scale pharmacogenomic data sets that catalogued the sensitivity of a large number of cancer cell lines to approved and potential drugs, and finds that whereas the gene expression data are largely concordant between the two studies, the reported drug sensitivity measures and subsequently their association with genomic features are highly discordant.

The ultraluminous X-ray source M 101 ULX-1 consists of a black hole orbiting a Wolf-Rayet star; optical spectroscopy now shows that the orbital period is 8.2 days, suggesting that the black hole has a mass in the range 5 to 30 solar masses, though the X-ray spectra are unlike what is expected from accretion onto a stellar-mass black hole—accretion must occur from captured stellar wind, which has hitherto been thought to be so inefficient that it could not power an ultraluminous source.