Articles in 2013

In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.

Determining major branches in the tree of life generally relies on concatenating as much genetic information as possible, but, as shown here, phylogenomic analysis often produces results that are incongruent with the results of concatenation; a method that gives credence to genes or internodes with high average internode support reduces the incongruence.

An experimental study of certain short-lived isotopes of radon and radium has found clear octupole deformation in the nuclei of the latter — that is, these nuclei are pear-shaped; the results enable discrimination between differing theoretical approaches to octupole correlations.

High-resolution cryo-EM density maps are used to present the structures of Drosophila and human 80S ribosomes in complex with eEF2, E-site transfer RNA and Stm1-like proteins, and reveal the presence of two additional structural layers in the ribosomes of metazoan eukaryotes.

Activation of IKK-β and NF-κB in the hypothalamus of mice is shown to accelerate the ageing process, leading to shortened lifespan; inhibition of hypothalamic or brain IKK-β and NF-κB delays ageing and increases lifespan, and NF-κB activation results in a reduction of GnRH levels, whereas NF-κB inhibition leads to GnRH-induced neurogenesis to mediate ageing retardation.

Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.

The crystal structure of the human smoothened (SMO) receptor is presented in complex with a small-molecule antitumour agent; this represents the first example of a non-class-A, 7-transmembrane (7TM) receptor structure, revealing different conserved motifs common within class frizzled 7TM receptors and an unusually complex arrangement of long extracellular loops stabilized by disulphide bonds.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Motor patterns underlying the rodent exploratory behaviours whisking and sniffing are coordinated by respiratory centres in the ventral medulla; a distinct region in the ventral medulla provides rhythmic input to the facial motor neurons that drive scanning by the vibrissae, and input from the pre-Bötzinger complex coordinates whisking with sniffing and basal breathing.

Small-angle scattering of X-rays or neutrons is more readily applied to macromolecular complexes than is X-ray crystallography, and is particularly useful for protein complexes with high flexibility; here new quantitative metrics are presented that will allow solution-derived structures to be validated and assessed for mass, resolution and accuracy.

A scheme is described that enables characterization and classical command of large quantum systems; it provides a test of whether a claimed quantum computer is truly quantum, and also advances towards a goal of quantum cryptography, namely the use of untrusted devices to establish a shared random key, with security based on the validity of quantum physics.

Here it is shown that ion flux through the TrkH–TrkA complex is upregulated by ATP and downregulated by ADP; solving the X-ray crystal structures of the tetrameric TrkA ring in the absence and presence of TrkH suggests a mechanism by which ATP-induced conformational changes in TrkA augment the activity of TrkH.

Genome sequencing and phylogenomic analysis show that the lungfish, not the coelacanth, is the closest living relative of tetrapods, that coelacanth protein-coding genes are more slowly evolving than those of tetrapods and lungfish, and that the genes and regulatory elements that underwent changes during the vertebrate transition to land reflect adaptation to a new environment.

It is known that compressed sequences of hippocampal place cells can ‘replay’ previous navigational trajectories in linearly constrained mazes; here, rat place-cell sequences representing two-dimensional spatial trajectories were observed before navigational decisions, and predicted the immediate navigational path.

This study reports the X-ray crystal structure of a Ktr K⁺ transporter; the structure of this KtrAB complex reveals how the dimeric membrane protein KtrB interacts with the cytosolic octameric KtrA regulatory protein.

High-resolution imaging has traditionally required thin sectioning, a process that disrupts long-range connectivity in the case of brains: here, intact mouse brains and human brain samples have been made fully transparent and macromolecule permeable using a new method termed CLARITY, which allows for intact-tissue imaging as well as repeated antibody labelling and in situ hybridization of non-sectioned tissue.

A new explanation for the origin of the accreted terranes that form the mountainous Cordillera of western North America is proposed and tested: stationary, intra-oceanic subduction deposited massive slab walls in the mantle and grew volcanic archipelagos at the surface, which were overridden by and accreted to North America during Cretaceous times.

The long-awaited structure of a telomerase holoenzyme, from Tetrahymena, has been obtained by electron microscopy; affinity labelling of subunits and modelling with NMR and crystal structures of various components allowed the identification of the catalytic core and subunit interactions, and the functional role of the subunits in telomerase processivity was enabled by performing the first reconstitution of the holoenzyme in vitro.

Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

A synthesis of geochemical proxy records of sea surface temperature shows that the early Pliocene climate was little different from today in terms of maximum ocean temperatures but had substantially lower meridional and zonal temperature gradients.