Research articles

During gene transcription, RNA polymerase (Pol) II moves forward along DNA and synthesizes mRNA. However, Pol II can also move backwards and stall, which is important for regulatory purposes or when the polymerase hits an obstacle such as a nucleosome. This arrested state is reactivated by the transcription factor TFIIS. Here, a crystal structure is presented of a backtracked yeast Pol II complex in which the backtracked RNA can be observed, plus a structure of a backtracked complex that contains TFIIS. A model is presented for Pol II backtracking, arrest and reactivation during transcription elongation.

The harmonic oscillator is a simple and ubiquitous physical system. This paper reports a new realization in the quantum regime, achieving direct controllable coupling between quantized mechanical oscillators. The oscillators are ions held in trapping potentials (separated by 40 micrometres) and coupled through their mutual Coulomb interaction. The system could be used as a building block for quantum computers and simulators.

As the rates of replication and transcription are different, the machineries that carry out these processes are bound to clash on DNA. In contrast to results from head-on collisions, co-directional encounters have been shown to have mild effects in vitro, requiring no additional replication restart factors. It is now shown that in bacterial cells, both types of events require the activities of restart proteins to resume replication when a transcription complex is encountered.

A quantum mechanical link between two mechanical oscillators has never been directly demonstrated. This study achieves direct coupling between single ions oscillating in traps separated over a distance of 54 micrometres. Additional ions are employed as antennae to amplify the coupling. The system may provide a building block for quantum computers and opportunities for coupling different types of quantum systems, such as trapped Rydberg atoms.

Here it is shown that during the silent phase of prion infection, prions first exponentially propagate until a defined limit is reached. Then a plateau phase follows. Prion propagation is independent of prion concentration, whereas in the plateau phase the time to clinical onset is inversely correlated to prion concentration. The similar levels of infectivity at the end of the first and second phase suggests that there is a separation between prion infectivity and toxicity. Moreover, something seems to limit prion production. It is suggested that the prions are not neurotoxic themselves but catalyse the formation of such species from PrP^C. Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity to a toxic pathway.

Droughts of tens of years are known to have occurred in the southwestern United States over the past two millennia, but model simulations suggest that much longer 'megadroughts' might occur in a future, warmer climate. So far, the presence of such droughts in the palaeoclimatic record has been unclear. Now, a lake sediment core from northern New Mexico is analysed, showing that millennial-scale megadroughts were a regular feature of Pleistocene interglacials. The results suggest that, in the absence of anthropogenic warming, the southwestern United States would probably be entering a cool and wet phase.

Substantial risk for schizophrenia is conferred by large copy number variants at a number of genomic loci. Here, a significant association between duplications on chromosome 7 and schizophrenia is reported. Importantly, microduplication analysis narrowed down the region to a region just upstream of a gene encoding vasoactive intestinal peptide receptor (VIPR2). Increased expression of VIPR2 in patients with schizophrenia implicates VIP signalling as a molecular mechanism underlying schizophrenia.

The 'Cambrian explosion', just over 500 million years ago, was a burst of evolution during which most kinds of animals we see today first appeared in the fossil record. They were, however, accompanied by a large number of creatures whose lineages were destined to disappear. Among these were the lobopodians, creatures vaguely related to modern arthropods and the velvet worms of tropical forests, and which — like velvet worms — looked more like worms with legs. Lobopodians came in a variety of bizarre forms, and the discovery of a lobopodian from the Cambrian of China adds to this group. It looked like a thin, flexible worm with oddly inappropriate, chunky, armoured legs. It is claimed that this creature was, however, the closest known fossil relative of modern arthropods, suggesting that the process of acquiring the robust external skeleton characteristic of the group started with the legs, and worked upwards from there.

Gram-negative bacteria expel toxic chemicals via tripartite efflux pumps spanning both the inner and outer membranes. A crystallographic model of this tripartite efflux complex has been unavailable because co-crystallization of different components of the system has proven to be extremely difficult. The X-ray crystal structure of CusA of the CusCBA tripartite efflux system from Escherichia coli has been reported previously, and here the X-ray crystal structure of the CusBA co-complex is reported. The structure reveals that the trimeric CusA efflux pump interacts with six CusB protein molecules at the upper half of the periplasmic domain, and the predicted structure of the trimeric CusC channel was used to develop a model of for the tripartite efflux complex.

Most models for volcanic tremor rely on specific properties of the geometry, structure and constitution of volcanic conduits as well as the gas content of the erupting magma. Here, a model is used of a silicic magma rising in a conduit as a columnar plug to demonstrate that, for most geologically relevant conditions, the magma column will oscillate or 'wag' against the restoring force of a highly vesicular annulus of sheared bubbles at observed tremor frequencies. The frequencies produced are relatively insensitive to the conduit structure and geometry.

Here it is shown that nanoparticles containing two Toll-like receptor ligands can boost the magnitude and persistence of vaccine-elicited antibody responses in primates, improving vaccine-mediated protection against influenza virus.

Little is known about how nutritional cues are detected by quiescent neural stem cells (neuroblasts in Drosophila melanogaster) and how these signals are relayed to reactivate their cell cycle to exit quiescence. This study uses an integrative physiology approach to identify the relay mechanism regulating this nutritional checkpoint in neural progenitors. It is found that specific insulin-like peptides produced within the brain by glia bridge the amino-acid/TOR-dependent signal derived from the fat body with PI3K/TOR signalling in neuroblasts to induce exit from quiescent.

Impressive progress has been achieved in isolating quantum systems from the environment and coherently controlling their dynamics. However, engineering the dynamics of many particles by a controlled coupling to an environment (in an 'open' quantum system) remains largely unexplored. Here, an approach is demonstrated based on ion-trap technology for simulating an open quantum system with up to five qubits. By adding controlled dissipation to coherent operations, the work offers novel prospects for open-system quantum simulation and computation.

It has recently been shown that neurons in the lateral habenula (LHb), a nucleus that projects to midbrain reward areas, can signal aversive outcomes and may be disrupted in depressive disorders. This study now shows that in rats exhibiting learned helplessness (a model of major depression) excitatory synapses onto LHb neurons are potentiated, and that this correlates with helplessness behaviour. Furthermore, depleting transmitter release by repeated electrical stimulation of LHb using a protocol similar to deep brain stimulation rescues both synaptic changes and learned helplessness behaviour.

A common stem cell is known to produce both neural plate and mesoderm, but the factors regulating this choice are unknown. This study determines that Tbx6-dependent modulation of the developmental transcription factor Sox2 drives the fate of axial stem cells. In the absence of Tbx6, cells aberrantly upregulated Sox2 activity, with the result that cells originally destined to be mesoderm turned into ectopic neural tubes. In the absence of the N1 enhancer, this aberrant regulation is corrected and cells follow the appropriate fate, even in the absence of Tbx6. Therefore, active repression of the neural fate program is essential for mesoderm tissue to develop from axial stem cells.

When did macroscopic, complex life forms first appear in the fossil record? This study presents spectacular fossils of seaweed-like forms from the approximately 600-million-year-old early Ediacaran of China, a time when the Earth had only just recovered from the worldwide Marinoan glaciation.

In the area of metamaterials it is shown that electromagnetic properties can be achieved that are not attainable with natural materials. The main research efforts have been directed towards experimentally realizing materials with negative refractive index, but to extend the potential and design flexibility for novel 'transformation optics' applications, it is of considerable interest to produce a material with unnaturally high refractive index. A broadband, flexible terahertz metamaterial with unprecedented high refractive index, reaching a value of 38.6, is now demonstrated.

The super-massive black holes of 10⁶ to 10⁹ solar masses that reside in the nuclei of active galaxies (AGN) are surrounded by a region emitting broad emission lines, probably associated with an accretion disk, which cannot be resolved spatially. The relative significance of inflow, outflow, rotational, or turbulent motions in the broad-line region as well as their structure (spherical and/or thin/thick accretion disk) are unknown. This study reports a fundamental relation between the observed emission line width and shape in AGN spectra, from which it is inferred that the geometry of the inner region is flattest for the fast-rotating broad-line objects whereas slow-rotating narrow-line AGN have a more spherical structure. Knowing the rotational velocities one can derive more accurately the central black hole masses, which are two to ten times smaller than previously estimated.