Letters in 2010

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.

Mitochondrial reactive oxygen species are shown to be required for activation of the NLRP3 inflammasome by various stimuli.

Three distinct models for the recently discovered super-Earth (masses 2–10 times that of Earth) planet GJ 1214b that are consistent with its mass and radius have been suggested. Breaking the degeneracy between these models requires obtaining constraints on the planet's atmospheric composition. Here, a ground based measurement of the transmission spectrum of GJ 1214b between 780 and 1,000 nm is reported. The lack of features in this spectrum rules out cloud free atmospheres composed primarily of hydrogen. If the planet's atmosphere is hydrogen-dominated, then it must contain clouds or hazes that are optically thick at pressures <200 mbar. Alternatively, the data are also consistent with the presence of a dense water vapour atmosphere.

A crystal structure of bacterial RNA polymerase (RNAP) bound to the transcription inhibitor Gfh1 reveals the mechanism of inhibition by Gfh1 and an alternative ratcheted state of RNAP.

Innate differences between male and female behaviours must be inscribed in their respective genomes, but how these encode distinct neuronal circuits remains largely unclear. Focusing on sex specific responses to the cVA pheromone in fruitflies, a chain of four successive neurons carrying olfactory signals down to motor centres has been identified, with all male to female anatomical differences lying downstream of a conserved sensory cell. The techniques developed should help others in the task of neuronal circuit mapping, which remains daunting even for the relatively simple fly brain.

During translation, tRNAs enter the ribosome and then move sequentially through three sites, known as A, P and E, as they transfer their attached amino acids onto the growing peptide chain. How the ribosome facilitates tRNA translocation between the sites remains largely unknown. Now a study uses multiparticle cryoelectron microscopy of a ribosome bound to the translation elongation factor, EF-G, to get information about tRNA movement. It identifies two new substates and sees that translocation is linked to unratcheting of the 30S ribosomal subunit.

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.

Multipotent stem cells expressing Lgr5 are known to generate all cell types of the intestinal epithelium (enterocytes, goblet cells, Paneth cells and enteroendocrine cells). A new study shows that Paneth cells have an essential role for intestinal crypt and stem cell maintenance by supplying essential niche signals to the Lgr5-expressing cells.

Here it is shown that reactivation of endogenous telomerase activity in mice extends telomeres, reduces DNA damage signalling, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease and the reversal of damage observed here support the development of regenerative strategies designed to restore telomere integrity.

The acceleration of the expansion of the Universe is attributed to a 'dark energy' component that opposes gravity. These authors report an analysis of the symmetry properties of distant pairs of galaxies from archival data. This allows them to determine that the Universe is flat, and by alternately fixing its spatial geometry and the dark energy equation-of-state parameter, w_X, they establish at the 68.3 per cent confidence level that −0.85 > w_X > −1.12 and 0.60 < Ω_X < 0.80, where Ω_X is the abundance of dark energy.

p53 is an important tumour suppressor gene. Two papers now show in a Kras-driven lung cancer model that p53-mediated tumour suppression is only engaged late during tumour progression, when the Kras oncogenic signal reaches a threshold sufficient to activate the ARF–p53 pathway. Therefore, p53 re-expression in p53-deficient lung tumours does not restrict early stages of tumorigenesis, but induces tumour regression of more aggressive tumours.

The development of table-top femtosecond electron diffraction sources in recent years has opened up a new way to observe atomic motions in crystalline materials undergoing structural changes. Here, the technique is used to study the charge density wave material 1T-TaS₂, where a modulation of the electron density is accompanied by a periodic lattice distortion. In this femtosecond electron diffraction experiment, where atomic motions are observed in response to a 140 femtosecond optical pulse, the periodic lattice distortion is found to collapse on an exceptionally fast timescale (about 250 femtoseconds), indicative of an electronically driven process involving a highly cooperative process.

Protein machineries that move along the DNA, such as DNA polymerases and helicases, will necessarily encounter other bound proteins interacting with specific sites. Using 'curtains' of labelled DNA, this study measured whether such bound proteins interfere with the activity of the bacterial DNA translocase RecBCD. The translocase is able to push the proteins over nonspecific sites for thousands of base pairs before they are displaced.

Masses of pulsating classical Cepheid supergiants derived from stellar pulsation theory are smaller than the masses derived from stellar evolution theory. An independent determination for a classical Cepheid in a binary system is needed to determine which is correct. These authors report the discovery of a classical Cepheid in the Large Magellanic Cloud. They determine the mass to a precision of one per cent and show that it agrees with its pulsation mass.

p53 is an important tumour suppressor gene. Two papers now show in a Kras-driven lung cancer model that p53-mediated tumour suppression is only engaged late during tumour progression, when the Kras oncogenic signal reaches a threshold sufficient to activate the ARF–p53 pathway. Therefore, p53 re-expression in p53-deficient lung tumours does not restrict early stages of tumorigenesis, but induces tumour regression of more aggressive tumours.