Articles in 2012

Nuclear genome transfer using unfertilized donor oocytes is performed and shown to be effective in preventing the transmission of mitochondrial DNA mutations; the swapped oocytes can develop to the blastocyst stage, and produce parthenogenetic embryonic stem-cell lines that show normal karyotypes and only mitochondrial DNA from the donor oocyte.

Recent developments that reduce the computational cost and scaling of wavefunction-based quantum-chemical techniques open the way to the successful application of such techniques to a variety of real-world solids.

An analysis of staged hagfish embryos shows that the hagfish adenohypophysis is ectodermal in origin, revealing it to be a developmental quirk unique to hagfishes that was hitherto misleading; from this and other observations a ‘pan-cyclostome’ developmental pattern is derived, indicating that it was primitive for all vertebrates.

Presenilin, the catalytic component of γ-secretase, cleaves amyloid precursor protein into short peptides that form the plaques that are found in the brains of patients with Alzheimer’s disease; here the structure of a presenilin homologue is described, which will serve as a framework for understanding the mechanisms of action of presenilin and γ-secretase.

An explicit theoretical construction of a metallic non-Fermi liquid ground state opens a route to attack long-standing problems such as the ‘strange metal’ phase of high-temperature superconductors.

An automated approach designing drug ligands to multi-target profiles (with a 75% prediction success rate) is experimentally validated by the invention of novel ligands tailored to the complex and physiologically-relevant goal of identifying drugs that can specifically target profiles of multiple proteins.

RNA-recognition elements are identified for the fragile-X-syndrome-associated RNA-binding protein FMRP, in addition to its target messenger RNAs; although many of FMRP gene targets discovered are involved in brain function and autism spectrum disorder, a proportion are also dysregulated in mouse ovaries, suggesting cross-regulation of signalling pathways in different tissues.

A Staphylococcus aureus leukotoxin targets cells expressing the chemokine receptor CCR5, a mechanism for the specificity of leukotoxins towards different immune cells.

The minimal possible requirement for AMPA receptor trafficking during long-term potentiation is explored, revealing that no region of the receptor subunit is necessary, in contrast with previous work; the only requirement for LTP seems to be a large reserve of glutamate receptors.

The X-ray crystal structure of the human G-protein-coupled receptor protease-activated receptor 1 (PAR1) bound to the antagonist vorapaxar is solved, revealing an unusual method of drug binding that should facilitate the development of improved PAR1-selective antagonists.

An X-ray crystal structure of the bacterial cellulose synthase captures the process of cellulose synthesis and membrane translocation; the structure indicates how the synthesis of cellulose and the translocation of the nascent polysaccharide chain across the cell membrane are coupled.

A framework for metagenomic variation analysis to explore variation in the human microbiome is developed; the study describes SNPs, short indels and structural variants in 252 faecal metagenomes of 207 individuals from Europe and North America.

A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

The human heart regenerates poorly, causing insufficient healing after injury; here, microRNAs screened for the ability to induce cardiomyocyte proliferation are shown to stimulate cardiac regeneration and almost complete recovery of the heart after infarction.

Recordings from rat grid cells, cells that are active at periodically spaced locations in the environment, show that they are organized into discrete modules that maintain distinct scale and orientation, and may respond independently to environmental changes.

The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria and plant chloroplasts; the crystal structure of TatC, an integral membrane protein and core component of this complex, is now presented.

Sequencing the nuclear genomes of Guillardia theta and Bigelowiella natans, transitional forms in the endosymbiotic acquisition of photosynthesis by engulfment of certain eukaryotic algae, reveals unprecedented alternative splicing for a single-celled organism (B. natans) and extensive genetic and biochemical mosaicism, shedding light on why nucleomorphs persist in these species but not other algae.

Sequencing of the hexaploid bread wheat genome shows that it is highly dynamic, with significant loss of gene family members on polyploidization and domestication, and an abundance of gene fragments.

Here it is shown that the NAD-dependent deacetylase SIRT2 is an essential component of necrosis, and that mouse hearts that do not contain SIRT2 or that are treated with a pharmacological inhibitor of SIRT2 are largely protected from ischaemic injury.

Global distributions of trace elements in ocean floor basalts are found to describe a systematic pattern that is due to cycling of magma through the global ensemble of magma chambers.