Articles in 2013

Analysis of the gut microbial gene composition in obese and non-obese individuals shows marked differences in bacterial richness between the two groups, with individuals with low richness exhibiting increased adiposity, insulin resistance, dyslipidaemia and inflammation; only a few bacterial marker species are needed to distinguish between individuals with high and low bacterial richness, providing potential for future diagnostic tools.

Cell-type-specific anthrax toxin receptor CMG2-null mice are generated and used to show that the Bacillus anthracis toxins lethal toxin (LT) and oedema toxin (ET) target distinct cell types; in contrast to previous suggestions, it is shown that endothelial cells are not key targets for either toxin and instead LT targets cardiomyocytes and vascular smooth muscle cells whereas ET targets hepatocytes.

Upon wounding, plants mount a systemic response resulting in the production of jasmonates, hormones that confer resistance to herbivores; here we identify genes necessary for the electrical activity that leads to jasmonate synthesis far from the wound itself.

This study shows that most known mediators of immunity, such as TLR2, MyD88, T cells or B cells, and neutrophils and monocytes, are dispensable for pain produced by Staphylococcus aureus infection; instead, bacterial products, such as N-formylated peptides and α-haemolysin, induce pain by directly activating nociceptor neurons, which in turn modulate inflammation.

An analysis of mutations from over 7,000 cancers of diverse origins reveals the diversity of mutational processes underlying the development of cancer; more than 20 distinct mutational signatures are described, some of which are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are specific to individual tumour types.

Here, the first genome-wide in vivo RNA interference screens in a mammalian animal model are reported: genes involved in normal and abnormal epithelial cell growth are studied in developing skin tissue in mouse embryos, and among the findings, β-catenin is shown to act as an antagonist to normal epithelial cell growth as well as promoting oncogene-driven growth.

Haramiyids were Mesozoic era animals that until now have been identified only from their distinctive teeth, and are thought to be related to the better-known multituberculates: here the authors describe a haramiyid that is very primitive in terms of its jaw and ankle characteristics, suggesting a lack of relationship to the multituberculates.

Cyclic AMP, one of the earliest discovered and most intensely studied signalling molecules in molecular biology, is widely believed to signal the carbon status in mediating catabolite repression in bacteria; here a quantitative approach reveals a much broader physiological role for cAMP signalling, whereby it coordinates the allocation of proteomic resources with the global metabolic needs of the cell, including, for example, nitrogen or sulphur.

Reconstruction of a connectome within the fruitfly visual medulla, containing more than 300 neurons and over 8,000 chemical synapses, reveals a candidate motion detection circuit; such a circuit operates by combining displaced visual inputs, an operation consistent with correlation based motion detection.

Improved electron microscopy methods are used to map a mammalian retinal circuit of close to 1,000 neurons; the work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations.

Whole transcriptome differential gene co-expression correlation analysis of cerebral cortex of APOE ε4 allele carriers and late-onset Alzheimer’s disease patients reveals an APOE ε4 carrier transcription network pattern that resembles that of late-onset Alzheimer’s disease and also identifies new genes of interest for further study.

Three structures of the eukaryotic small ribosomal subunit in complex with initiator tRNA, mRNA and the initiation factors eIF1 and eIF1A have been solved; these structures offer insight into the contributions of the initiation factors, the mechanism by which mRNA is scanned, and the interactions that occur in the ribosome’s P site.

A muscle-specific membrane protein called myomaker is transiently expressed during myogenesis and is both necessary and sufficient to drive myoblast fusion in vivo and in vitro.

LRG1 is identified as a new regulator of TGF-β signalling that promotes angiogenesis via a TβRII–ALK1–ENG–Smad1/5/8 signalling pathway; antibody-mediated inhibition of LRG1 reduces pathogenic neovascularization in a mouse model of retinal injury.

This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down’s syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down’s syndrome and for research into gene therapies.

Approximately 30% of known drugs target G protein-coupled receptors (GPCRs), but all the published structures of GPCRs to date are from the class A family of GPCRs; here the first X-ray crystal structure of a member of the class B family of GPCRs, the human corticotropin-releasing factor receptor 1, is determined.

Solitons — solitary waves that maintain their shape as they propagate — in a strongly interacting superfluid of fermionic lithium atoms are found to have an effective mass more than 50 times larger than the theoretically predicted value, a sign of strong quantum fluctuations.

Sensitive protein sensors of calcium have been created; these new tools are shown to report neural activity in cultured neurons, flies and zebrafish and can detect single action potentials and synaptic activation in the mouse visual cortex in vivo.

The X-ray crystal structure of the human glucagon receptor, a potential drug target for type 2 diabetes, offers a structural basis for molecular recognition by class B G-protein-coupled receptors.

Uncultivated archaeal and bacterial cells of major uncharted branches of the tree of life are targeted and sequenced using single-cell genomics; this enables resolution of many intra- and inter-phylum-level relationships, uncovers unexpected metabolic features that challenge established boundaries between the three domains of life, and leads to the proposal of two new superphyla.