Letters in 2008

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.

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.

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.

Repeated exposure to pathogens and generation of T-cell memory is thought to result in attrition of the pre-existing memory T cell pool to maintain the overall size of the memory compartment constant. This work shows that new effector memory cells can be generated in large numbers without greatly impacting pre-existing memory.

Living in noisy colonies, songbird vocal learning requires individuals to differentiate self-generated vocalizations from other sound sources to accurately match the learned song template. However, neurons responding to vocal output have not been identified. This study identifies neurons in the auditory forebrain of zebra finch that specifically responded to either song or playback perturbations, suggesting the existence of a computational error-checking function in the forebrain auditory areas.

Dendritic spine morphogenesis is sensitive to experience-dependent plasticity, but whether or not experience-induced structural changes outlast the experience itself is unknown. This paper reveals that long-lived spine density increases in response to monocular deprivation that persist beyond the duration of time the eye was closed. Subsequent deprivation fails to induce further spine density increases, suggesting initial experience may provide a structural experience 'trace' that could be utilized in response to further functional shifts.