Regulation of p53 activity through lysine methylation

p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase.     

Recent and episodic volcanic and glacial activity on Mars revealed by the High Resolution Stereo Camera

The large-area coverage at a resolution of 10-20 metres per pixel in colour and three dimensions with the High Resolution Stereo Camera Experiment on the European Space Agency Mars Express Mission has made it possible to study the time-stratigraphic relationships of volcanic and glacial structures in unprecedented detail and give insight into the geological evolution of Mars. Here we show that calderas on five major volcanoes on Mars have undergone repeated activation and resurfacing during the last 20 per cent of martian history, with phases of activity as young as two million years, suggesting that the volcanoes are potentially still active today. Glacial deposits at the base of the Olympus Mons escarpment show evidence for repeated phases of activity as recently as about four million years ago. Morphological evidence is found that snow and ice deposition on the Olympus construct at elevations of more than 7,000 metres led to episodes of glacial activity at this height. Even now, water ice protected by an insulating layer of dust may be present at high altitudes on Olympus Mons.     

Single-exciton optical gain in semiconductor nanocrystals

Nanocrystal quantum dots have favourable light-emitting properties. They show photoluminescence with high quantum yields, and their emission colours depend on the nanocrystal size--owing to the quantum-confinement effect--and are therefore tunable. However, nanocrystals are difficult to use in optical amplification and lasing. Because of an almost exact balance between absorption and stimulated emission in nanoparticles excited with single electron-hole pairs (excitons), optical gain can only occur in nanocrystals that contain at least two excitons. A complication associated with this multiexcitonic nature of light amplification is fast optical-gain decay induced by non-radiative Auger recombination, a process in which one exciton recombines by transferring its energy to another. Here we demonstrate a practical approach for obtaining optical gain in the single-exciton regime that eliminates the problem of Auger decay. Specifically, we develop core/shell hetero-nanocrystals engineered in such a way as to spatially separate electrons and holes between the core and the shell (type-II heterostructures). The resulting imbalance between negative and positive charges produces a strong local electric field, which induces a giant ( approximately 100 meV or greater) transient Stark shift of the absorption spectrum with respect to the luminescence line of singly excited nanocrystals. This effect breaks the exact balance between absorption and stimulated emission, and allows us to demonstrate optical amplification due to single excitons.     

MARSIS radar sounder evidence of buried basins in the northern lowlands of Mars

A hemispheric dichotomy on Mars is marked by the sharp contrast between the sparsely cratered northern lowland plains and the heavily cratered southern highlands. Mechanisms proposed to remove ancient crust or form younger lowland crust include one or more giant impacts, subcrustal transport by mantle convection, the generation of thinner crust by plate tectonics, and mantle overturn following solidification of an early magma ocean. The age of the northern lowland crust is a significant constraint on these models. The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) instrument on the European Space Agency's Mars Express spacecraft is providing new constraints on the martian subsurface. Here we show evidence of buried impact basins ranging in diameter from about 130 km to 470 km found over approximately 14 per cent of the northern lowlands. The number of detected buried basins >200 km in diameter indicates that the lowland crust is ancient, dating back to the Early Noachian epoch. This crater density is a lower limit because of the likelihood that not all buried basins in the area surveyed by MARSIS have been detected. An Early Noachian age for the lowland crust has been previously suggested on the basis of a large number of quasi-circular topographic depressions interpreted to be evidence of buried basins. Only a few of these depressions in the area surveyed by MARSIS, however, correlate with the detected subsurface echoes. On the basis of the MARSIS data, we conclude that the northern lowland crust is at least as old as the oldest exposed highland crust. This suggests that the crustal dichotomy formed early in the geologic evolution of Mars.     

The complex of tmRNA-SmpB and EF-G on translocating ribosomes

Bacterial ribosomes stalled at the 3' end of malfunctioning messenger RNAs can be rescued by transfer-messenger RNA (tmRNA)-mediated trans-translation. The SmpB protein forms a complex with the tmRNA, and the transfer-RNA-like domain (TLD) of the tmRNA then enters the A site of the ribosome. Subsequently, the TLD-SmpB module is translocated to the P site, a process that is facilitated by the elongation factor EF-G, and translation is switched to the mRNA-like domain (MLD) of the tmRNA. Accurate loading of the MLD into the mRNA path is an unusual initiation mechanism. Despite various snapshots of different ribosome-tmRNA complexes at low to intermediate resolution, it is unclear how the large, highly structured tmRNA is translocated and how the MLD is loaded. Here we present a cryo-electron microscopy reconstruction of a fusidic-acid-stalled ribosomal 70S-tmRNA-SmpB-EF-G complex (carrying both of the large ligands, that is, EF-G and tmRNA) at 8.3?? resolution. This post-translocational intermediate (TI(POST)) presents the TLD-SmpB module in an intrasubunit ap/P hybrid site and a tRNA(fMet) in an intrasubunit pe/E hybrid site. Conformational changes in the ribosome and tmRNA occur in the intersubunit space and on the solvent side. The key underlying event is a unique extra-large swivel movement of the 30S head, which is crucial for both tmRNA-SmpB translocation and MLD loading, thereby coupling translocation to MLD loading. This mechanism exemplifies the versatile, dynamic nature of the ribosome, and it shows that the conformational modes of the ribosome that normally drive canonical translation can also be used in a modified form to facilitate more complex tasks in specialized non-canonical pathways.     

Metal-insulator transition in chains with correlated disorder

According to Bloch's theorem, electronic wavefunctions in perfectly ordered crystals are extended, which implies that the probability of finding an electron is the same over the entire crystal. Such extended states can lead to metallic behaviour. But when disorder is introduced in the crystal, electron states can become localized, and the system can undergo a metal-insulator transition (also known as an Anderson transition). Here we theoretically investigate the effect on the physical properties of the electron wavefunctions of introducing long-range correlations in the disorder in one-dimensional binary solids, and find a correlation-induced metal-insulator transition. We perform numerical simulations using a one-dimensional tight-binding model, and find a threshold value for the exponent characterizing the long-range correlations of the system. Above this threshold, and in the thermodynamic limit, the system behaves as a conductor within a broad energy band; below threshold, the system behaves as an insulator. We discuss the possible relevance of this result for electronic transport in DNA, which displays long-range correlations and has recently been reported to be a one-dimensional disordered conductor.