Research articles

On rough metallic surfaces hotspots appear under optical illumination that concentrate light to tens of nanometres. This effect can be used to detect molecules, as weak fluorescence signals are strongly enhanced by the hotspots. Such hotspots are associated with localized electromagnetic modes, caused by the randomness of the surface texture, but the detailed profile of the local electromagnetic field is unknown. Here, an ingenious approach is described, making use of the Brownian motion of single molecules to probe the local field. The study succeeds in imaging the fluorescence enhancement profile of single hotspots on the surface of aluminium thin-film and silver nanoparticle clusters with accuracy down to one nanometre, and finds that the field distribution in a hotspot follows an exponential decay.

The HIV virion has a cone-shaped core composed of capsid proteins, which take either pentameric or hexameric form. The crystal structure of the capsid hexamer had been solved previously. Now the structure of the pentamer is provided, which allows the proposal of the first atomic-level model of the mature HIV capsid.

A novel technique called native elongating transcript sequencing (NET-seq) is described, which can quantify transcription with single nucleotide resolution. It is based on sequencing nascent transcripts associated with RNA polymerase II that are captured directly from live cells, and is used to gain insights into polymerase pausing and backtracking and the directionality of transcription.

Analysing human B-cell acute lymphoblastic leukaemias, this study maps the genetic heterogeneity of cells within a given tumour sample and the evolutionary path by which different subclones have emerged. Leukaemia-initiating cells that transplant the disease mirror the genetic variegation of the bulk tumours, providing insights into the heterogeneity of these functional subpopulations at the genetic level. This has implications for therapeutic approaches targeting the tumours and specifically leukaemia-initiating cells.

Ultraviolet (UV) exposure has been implicated in melanoma formation. Here it is shown, in a mouse model, that UVB induces the recruitment of macrophages which produce interferon-γ to promote melanomagenesis. The study suggests that in melanomas, interferon-γ could be targeted therapeutically.

Agriculture has been central to the success of humans and some social insects. This paper shows that social amoebae can do it too. Some isolates of Dictyostelium discoideum refrain from consuming all the available bacteria at a site and instead they incorporate them into their reproductive assemblages to seed a new bacterial crop at another location.

This paper shows that the activity of human beta-defensin 1 is regulated by its redox status, with enhanced antibiotic killing activity under reducing conditions as they are found in the distal colon. This is believed to serve to protect the healthy intestinal epithelium against potentially harmful colonization by commensal bacteria and opportunistic fungi. In vitro evidence implicates thioredoxin as the likely reducing agent.

The mechanism of action of general anaesthetics is poorly understood, although there is some evidence that their principal protein targets are pentameric ligand-gated ion channels (pLGICs). Here, the X-ray crystal structures of propofol and desflurane bound to a bacterial homologue of the pLGIC family are solved. The structures reveal a common binding site for these two anaesthetics in the upper part of the transmembrane domain of each protomer.

O GlcNAc transferase (OGT) is an essential mammalian enzyme that glycosylates proteins with O-linked β-N-acetylglucosamine (O-GlcNAc), and this regulates a variety of cellular signalling pathways. Here, the crystal structure of human OGT as a binary complex with UDP and a ternary complex with UDP and a peptide substrate is presented. The structures show how OGT recognizes peptide sequences and provide information on the enzymatic mechanism.

Long QT syndrome (LQTS) is a life-threatening congenital arrhythmogenic disease. This study models type-2 LQTS, which is caused by a mutation in the potassium-channel-encoding KCNH2 gene, by using induced pluripotent stem cell technology to generate cardiomyocytes from the fibroblasts of an individual diagnosed with the syndrome. The cells were used to screen a variety of drugs for either amelioration or aggravation of the disease phenotype, demonstrating the power of this approach for drug development and for patient-specific safety screening.

Here, the X-ray crystal structure of the β₁ adrenergic receptor, a G-protein-coupled receptor, bound to four small molecules that either act as full agonists or partial agonists is solved. The structures show that agonist binding induces a contraction of the catecholamine-binding pocket relative to the antagonist-bound receptor. This work reveals the pharmacological differences between different ligand classes, which should facilitate the structure-based design of new drugs with predictable efficacies.

Massive clusters of galaxies have been found as early as 3.9 billion years after the Big Bang. Cosmological simulations predict that these systems should descend from 'protoclusters' — early overdensities of massive galaxies that merge hierarchically to form a cluster. Observational evidence for this picture, however, is sparse because high-redshift protoclusters are rare and difficult to observe. Here, a protocluster region 1 billion years (z = 5.3) after the Big Bang is reported. This cluster extends over >13 megaparsecs, contains a luminous quasar as well as a system rich in molecular gas. A lower limit of >4 × 10¹¹ solar masses of dark and luminous matter in this region is placed, consistent with that expected from cosmological simulations.

The reversible transfer of quantum states of light into and out of matter constitutes an important building block for future applications of quantum communication. Here, the reversible transfer of photon–photon entanglement into entanglement between a photon and a collective atomic excitation in a solid-state device is reported. This should simplify frequency-matching of light with matter interfaces in advanced applications of quantum communication, bringing fully quantum-enabled networks a step closer.

The observed number counts of high-redshift galaxy candidates have been used to build up a statistical description of star-forming activity at redshift of about z>7. Here it is reported that gravitational lensing is likely to dominate the observed properties of galaxies with redshifts of about z>12, when the instrumental limiting magnitude is expected to be brighter than the characteristic magnitude of the galaxy sample. The number counts could be modified by an order of magnitude. Future surveys will need to be designed to account for a significant gravitational lensing bias in high-redshift galaxy samples.

Harnessing entanglement between light and material systems is of interest for future quantum information technologies. Here, entanglement is demonstrated between a photon at the telecommunication wavelength (1,338 nm) and a single collective atomic excitation stored in a crystal. These resources pave the way for building multiplexed quantum repeaters for long-distance quantum networks.

This study measures 'puddles' of charge in a fractional quantum Hall device and finds new evidence for the existence of quarter charge particles, thereby boosting confidence in the prospects for topological quantum computation.

This study shows that across-strike and along-strike changes in crustal properties at the Eastern Lau spreading centre are large and abrupt, implying correspondingly large discontinuities in the nature of the mantle supplying melt to the ridge axes. It is concluded that stable, broad triangular upwelling regions, as inferred for mid-ocean ridges, cannot form near the mantle wedge corner. Instead, the observations imply a dynamic process in which the ridge upwelling zone preferentially captures water-rich low-viscosity mantle when it is near the arc. As the ridge moves away from the arc, a tipping point is reached at which that material is rapidly released, resulting in rapid changes in the character of the crust formed at the ridge.

Much of what we know about the behaviour of animals in the wild comes from studies in which individual animals are marked for identification purposes. But can the marking itself affect the outcome? This study shows that it does. In a ten-year study on king penguins in the Antarctic, penguins sporting identification bands on their wings had significantly lower long-term fitness than unmarked penguins. This study should give pause for thought to researchers seeking to discover the behaviour of animals in the wild.

The X-ray crystal structure of the human β₂ adrenergic receptor, a G-protein-coupled receptor, in an agonist-bound 'active' state is solved. Comparison of this structure with a previously published structure of the same GPCR in an inactive state indicates that minor changes in the binding pocket of the protein lead to major changes elsewhere — there is a large outward movement of the cytoplasmic end of one of the transmembrane segments and rearrangements of two other transmembrane segments. This structure provides insights into the process of agonist binding and activation.

Neuronal plasticity is thought to be the source of several chronic neurological conditions, including tinnitus. Using a rodent model for noise-induced tinnitus, this study finds that reversing neural plasticity induced by the tinnitus can correct perceptual impairments caused by the ailment. Pairing tones with stimulation of the vagus nerve sharpened auditory neuron tuning and eliminated the physiological as well as behavioural correlates of the tinnitus. This proof of principle suggests that simply restoring normal neural activity to circuits that have been pathologically modified could provide a benefit in those ailments involving aberrant neural plasticity.