Research articles

The 2.4 Å structure of the Ca²⁺-bound calpain 2 heterodimer bound to one of the four inhibitory domains of calpastatin. Calpastatin seems to inhibit calpain by occupying both the primed and unprimed sides of the active site cleft. This crystal structure also reveals the conformational changes that calpain undergoes upon binding calcium, which include opening of the active site cleft and movement of the domains relative to each other to produce a more compact enzyme.

It is shown that mice lacking the renal Rhcg factor have impaired ammonium excretion, thereby refuting the long-standing notion that rapid transepithelial transport of non-ionic ammonia occurs solely by lipid phase diffusion. In addition, it is shown that Rhcg is required for epididymal fluid homeostasis with clear consequences for male fertility.

This paper reports an excess of galactic cosmic-ray electrons at energies of ∼300-800 GeV, which indicates a nearby source of energetic electrons. Such a source could be an unseen astrophysical object that accelerates electrons to those energies, or the electrons could arise from the annihilation of dark matter.

This paper presents simulations with a coupled model of glacial climate and biogeochemical cycles, forced only with changes in the Atlantic meridional overturning circulation. It is found that variations in atmospheric carbon dioxide levels on millennial time scales are dominated by slow changes in the deep ocean inventory of biologically-sequestered carbon and are correlated to Antarctic temperature and Southern Ocean stratification. The results suggest that ocean circulation changes were the primary mechanism that drove glacial fluctuations in carbon dioxide and nitrous oxide fluctuations on millennial time scales.

A four-stranded DNA intermediate, known as a Holliday junction, is formed during meiosis and DNA repair. This structure covalently links two DNA molecules. The product of the RuvC gene in Escherichia coli was shown to be the bacterial Holliday junction resolvase. The mammalian enzyme has remained refractory to identification until now, where GEN1 is identified as the human resolvase.

The 3.0 Å structure of Ca²⁺-bound m-calpain in complex with the first calpastatin repeat is solved, revealing the mechanism of the exclusive specificity. The structure highlights the complexity of calpain activation by Ca²⁺, illustrating key residues in a peripheral domain that serve to stabilize the protease core after Ca²⁺-binding.

This is the first report of the sequencing of the nearly complete nuclear genome of an extinct animal, the woolly mammoth. 4.1 billion bases of high quality sequence from several mammoth species are reported, including 3.3 billion bases from the woolly mammoth. Nuclear-genome sequencing of extinct species and its comparison with the extant relatives (in this case African elephant) provide insights into elephantid evolution and population differences.

This paper presents the crystal structures of an intact nuclear receptor complex—the heterodimer of PPAR-γ and RXR-α bound to DNA, ligands and coactivator peptides.

Several species are observed to expand their habitat range towards cooler, higher latitude environments as a result of climate warming. It is shown that plant migrations can lead to successful invasions due to their relatively low susceptibility to native soil pathogens and herbivores.

Complex visual scenes are made up of many component features, such as edges and textures. Neurons in early stages of the visual system are sensitive to individual features, and it is implicitly believed that the nervous system must put them back together to signal conjunctions of different features, but how this is achieved is unknown. This paper proposes a model in which neural activity encodes statistical variations of features in images, thereby allowing the visual system to generalize across variable images.

Inflammatory heptocellular adenomas (IHCAs) show activation of an acute-phase inflammatory response signalling pathways, and it is found that this is due to gain-of function mutations in the IL6ST gene encoding gp130, a coreceptor for IL-6 and other cytokines that activate inflammatory signalling pathways. These mutations lead to constitutive activation of STAT3 signalling, contributing to the inflammatory phenotype of IHACs.

Head-on collision between the replication and transcription machineries halts DNA synthesis. This work examines what happens when a replisome bumps up against an engaged RNA polymerase. The study finds that the RNA polymerase is displaced from the DNA, but the replisome and the nascent mRNA remain attached. A replication assembly factor, the β-clamp, finds the 3′ end of the mRNA and recruits the still-bound replisome, which exploits the mRNA as a primer to reinitiate DNA synthesis.

The classical pentraxins, serum amyloid P component (SAP) and C-reactive protein (CRP), are major acute phase reactants in mouse and man. It is shown that pentraxins recognize various FcγRs and SAP opsonization activates FcγR-mediated phagocytosis and cytokine secretion. The receptor binding sites for SAP and IgG overlap, resulting in competition of IgG binding to FcγR as well as inhibition of immune complex-mediated phagocytosis by soluble pentraxins.

This paper discloses a new class of chiral catalysts that initiate olefin metathesis with exceptional efficiency and enantioselectivity. These new catalysts bear a stereogenic metal centre and carry only monodentate ligands; the molybdenum-based complexes are rendered non-racemic by a stereoselective ligand exchange process involving an enantiomerically pure aryloxide, a class of ligands rarely used in asymmetric catalysis.

In Drosophila more than 95% of the genes have remained on the same chromosome arm in 12 species that diverged 63 Myr ago.

This study finds that only a quarter of D. melanogaster Y linked genes are also Y-linked in these 12 species. Gene losses are known to play a major role in the evolution of Y chromosomes, but this study shows that in contrast with the mammalian Y, gene gains play an important role in the evolution of the Drosophila Y chromosome.

This study shows that Myc-driven tumourigenesis is dependent on its ability to increase protein synthesis, as haploinsufficiency in ribosomal proteins decreases Myc-induced tumour formation. However, tumours caused by the loss of p53, were not affected. Myc stimulates cap-dependent protein translation at the expense of IRES-dependent translation, leading to the synthesis of a different set of proteins, and this effect is reversed by ribosomal protein haploinsufficiency.

CD8⁺ T cells are shown to induce vascular leakage in acute viral meningitis not by killing specific target cells, but by recruiting neutrophils and monocytes to the blood–brain barrier.