Research articles

For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed yeast pheromone communication to achieve complex computation through communication between individual cells performing simple logic functions. Such extracellular 'chemical wiring' is one promising way to get around intracellular noise when building more complex genetic circuitry.

Medulloblastomas are the most common malignant childhood brain tumours and are thought to arise from the cerebellum. There is substantial heterogeneity among medulloblastomas and some are thought to arise following aberrant Sonic Hedgehog pathway activation. It is now shown that a distinct subtype of medulloblastoma arises from the dorsal brainstem and is associated with altered WNT signalling. Distinct molecular and clinical profiles of the subtypes have implications for future treatment.

A primordial carbon-to-oxygen ratio (C/O) greater than 0.8 in an exoplanet causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmospheres also can differ from those in the Solar System. The solar C/O is 0.54. This study reports an analysis of spectra from the transiting hot Jupiter WASP-12b that reveals that C/O>1 in its atmosphere, based upon the observed concentrations of the prominent molecules CO, CH₄ and H₂O.

High-contrast near-infrared imaging of the nearby star HR 8799 has shown three giant planets. Here, the presence of a fourth planet, interior to and about the same mass as the other three, is reported. The system, with this additional planet, represents a challenge for current planet formation models as none of them can explain the in situ formation of all four planets.

Increased melting is often assumed to cause acceleration of ice sheets and glaciers through basal lubrication, possibly leading to increased rates of sea level rise. Now a physically-based model challenges this view, illustrating that above a critical threshold, increased melt will suppress the dynamic thinning process. Short-term spikes in water delivery, as from lake drainage or precipitation, still have the potential to generate spikes in velocity, but overall increases in melt do not appear likely to cause velocity increases.

For two hundred years, scientists have noticed that the appearance of embryos in related species converge in their appearance mid-way in development, diverging thereafter. But is this 'phylotypic stage' real, and how is it connected with the genetic basis of development? This issue is looked at in microcosm, concentrating on gene expression during the development of six species of the fruitfly Drosophila. It is shown that the genes expressed during the phylotypic stage are more conserved across the genus, supporting the age-old model.

For synthetic biologists' creativity to be unleashed, basic circuits must become truly interchangeable, that is, modular and scalable. This study, one of two linked papers, has harnessed bacterial 'quorum sensing' to achieve complex computation through communication between individual cells performing simple logic functions. Such extracellular 'chemical wiring' is one promising way to get around intracellular noise when building more complex genetic circuitry.

Humans and animals readily learn to associate neutral cues paired with rewards, but the exact role that dopamine release has in this learning is controversial. Using previously established rat strains selectively bred for many generations to have greater or lesser propensity to assign value to learned cues, this study uses cyclic voltammetry to measure dopamine signals in the different strains and also examines the effect of blocking dopamine. It is concluded that dopamine selectively mediates motivational, rather than predictive, aspects of the cues.

For two hundred years, scientists have noticed that the appearance of embryos in related species converge in their appearance mid-way in development, diverging thereafter. But is this 'phylotypic stage' real, and how is it connected with the genetic basis of development? Here, a method linking the genes transcribed at various stages of development (the transcriptome) with the evolutionary history of those genes is used. Genes transcribed in the phylotypic stage are, in evolutionary terms, the oldest and most conserved. This suggests that the phylotypic stage does represent the body plans of related species at their most unadorned, selection having sculpted the earlier and later stages of embryonic form to suit the particulars of each creature.

In the retina, highly selective wiring from inhibitory cells contributes to determine the direction-selection characteristics of an individual ganglion cell, yet how the asymmetric wiring inherent to these connections is established was unknown. Here, two independent studies using complementary techniques, including pharmacology, electrophysiology and optogenetics, find that although inhibitory inputs to both sides of the direction-selective cell are uniform early in development, by the second postnatal week, inhibitory synapses on the null side strengthen whereas those on the preferred side remain constant. These plasticity changes occur independent of neural activity, indicating that a specific developmental program is executed to produce the direction-selective circuitry in the retina.

This study introduces a novel recording technique for simultaneously measuring excitatory and inhibitory conductances of retinal ganglion cells to show that excitatory and inhibitory inputs are strongly correlated, thereby cancelling each other. Furthermore, dynamic clamp is used to introduce these conductance changes into the cell with or without correlations, and it is found that, as predicted by theoretical work, correlations significantly increase reliability of the spiking response.

Here, a comprehensive study of the sodium/galactose transporter (vSGLT) is presented, consisting of molecular dynamics simulations, biochemical characterization and a new crystal structure of the 'inward-open' conformation. These experiments show that sodium exit causes a reorientation of transmembrane helix 1, opening an inner gate required for substrate exit, while also triggering minor rigid-body movements in two sets of transmembrane helical bundles. This cascade of conformational changes is responsible for the proper timing of ion and substrate release.

The positive relationship between biodiversity and ecosystem function is well established, but the specific shape of the relationship can vary. Here, experimental evolution is used to show that the strength and slope depends on evolutionary history, with specialists and generalists that have evolved from the same ancestor giving rise to different diversity–function relationships.

Here, single nucleotide variants within the LMO1 locus are shown to be associated with inherited susceptibility to neuroblastoma, a childhood cancer of the sympathetic nervous system. Acquired structural variation in the same locus was also frequently found in neuroblastoma patients, leading to the suggestion that loci identified through genome-wide association studies might be also prone to somatic alterations and therefore identify potential therapy targets and/or biomarkers of tumour aggressiveness.

The E1 and E2 glycoproteins of alphaviruses form heterodimers and assemble into spikes on the virus surface, which mediate receptor binding and endocytosis. When the virion encounters acidic pH in the endosome E1 and E2 dissociate and E1 triggers fusion with the endosomal membrane. Two papers now provide the first crystal structures for glycoprotein complexes incorporating E2 at acidic and neutral pH, respectively. Together they provide insight into how fusion activation is controlled in alphaviruses.

Here it is shown that the ratio of zinc to total iron content constrains the valence state of iron in primary arc basalts and their mantle sources. Primitive arc magmas have identical Zn/Fe_T ratios (Fe_T = Fe²⁺ + Fe³⁺) as mid-ocean-ridge basalts, indicating a similar iron oxidation state of primary mantle melts in arcs and ridges and that the subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. It is concluded that the observed higher oxidation states of arc lavas must therefore be, in part, a consequence of shallow-level differentiation processes.

Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here, and in two accompanying studies, it is shown that the tumour suppressor Lkb1 has a crucial role in maintaining energy homeostasis in haematopoietic cells.

A long-standing question has been the interplay between pseudogap, which is generic to all hole doped copper oxide superconductors, and stripes, whose static form occurs in only one family of copper oxides over a narrow range of the phase diagram. This study reports observations of the spatial reorganization of electronic states with the onset of the pseudogap state at T^* in the high temperature superconductor Bi₂Sr₂CaCu₂O_8+x using scanning tunnelling microscopy. The onset of the pseudogap phase coincides with the appearance of electronic patterns that have the predicted characteristics of fluctuating stripes. The experiments indicate that stripes are a consequence of pseudogap behaviour rather than its cause.

The stellar initial mass function describes the mass distribution of stars at the time of their formation. This study reports observations of the Na I doublet and the Wing-Ford molecular FeH band in the spectra of elliptical galaxies. These lines are strong in stars with masses <0.3 solar masses and weak or absent in all other types of stars. The direct detection of the light of low-mass stars implies that they are very abundant in elliptical galaxies, making up >80% of the total number of stars and contributing >60% of the total stellar mass.