Articles in 2013

By combining lineage tracing with intravital microscopy, the position of a stem cell within its extended mouse hair follicle niche is shown to control its long-term fate and behaviour; laser ablation to remove restricted cell populations shows that bulge stem cells are dispensable for hair regeneration, and non-hair epithelial cells may change their fate to compensate and sustain hair growth.

Several irregularly shaped craters located within Arabia Terra, Mars, are interpreted as a new type of highland volcanic construct, similar to supervolcanoes on Earth, fundamentally changing the picture of ancient volcanism and climate evolution on Mars.

The olfactory receptors and neurons that recognize the insect repellent DEET have been identified in Drosophila melanogaster, enabling identification of new insect repellents in a chemical screen and offering another research avenue against diseases transmitted by insects.

The primary cilium is a microtubule-based organelle that functions in sensory and signal transduction; here the authors show that the primary cilium is required for activation of starvation-induced autophagy and that basal autophagy negatively regulates ciliogenesis.

X-ray crystal structures of Na⁺,K⁺-ATPase in a transition state that precedes the phosphorylated intermediate are described, showing how this ATPase functions as a Na⁺-specific pump.

A heat-pipe model of Earth, whereby interior heat is brought to the surface through localized channels, yields predictions that agree with craton data and the detrital zircon record, and offers a global geodynamic framework in which to explore Earth’s evolution before the onset of plate tectonics.

Although the origin of jaws is one of the key episodes in the evolution of vertebrates, the jaw bones of modern bony fishes and limbed vertebrates differ so much from those in any other groups that the individual evolutionary steps in the transition are still unknown; here Entelognathus is described, an early placoderm fish with full body armour, but with marginal jaw bones similar to those of modern bony fishes and limbed vertebrates.

A novel genomic technique, single-cell Hi-C, detects thousands of simultaneous chromatin contacts in a single cell; this is used to show that individual chromosomes maintain domain organization at the megabase scale, but that chromosome structures vary from cell to cell at larger scales.

This study investigates how zygotic transcription is initiated and the maternal transcripts cleared in the zebrafish embryo: using loss-of-function analyses, high-throughput transcriptome sequencing and ribosome footprinting, the important roles of pluripotency factors Nanog, Pou5f1 and SoxB1 during these processes are identified.

This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.

The ChIP-exo technique is used to map the organization of transcription initiation complexes across the human genome at near-base-pair resolution; most of the transcription initiation complexes give rise to non-coding, non-polyadenylated RNA, indicating that pervasive non-coding transcription arise from specific promoters and is regulated.

Sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project reveal widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent, and the analyses point to putative causal variants for dozens of disease-associated loci.

The X-ray crystal structure of the Drosophila dopamine transporter bound to the antidepressant drug nortriptyline is presented, providing the first crystal structure of a eukaryotic neurotransmitter sodium symporter.

Induced pluripotent stem cells (iPS cells) have been created in vivo by reprogramming mouse somatic cells with Oct4, Sox2, Klf4 and c-Myc; these cells have totipotent features that are missing from in vitro created iPS cells or embryonic stem cells.

In male mice oxytocin acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression (LTD) of excitatory synaptic transmission in medium spiny neurons; deletion of oxytocin receptors from the dorsal raphe nucleus, which provides serotonergic innervation of the NAc, and blockade of NAc serotonin 1B receptors both prevent oxytocin-induced LTD and social reward.

An analysis of somatic tissues derived from mouse models of Down’s syndrome shows reduced self-renewal capacities in various cell types, with these defects partially dependent on triplication of the Usp16 gene; overexpression and knockout studies in human cells shows that USP16 has a role in Down’s syndrome-related proliferation defects, making this gene an attractive option for further study.

Mutations in the ubiquitin ligase parkin are associated with increased susceptibility to Parkinson’s disease; parkin is already known to have a role in mitophagy and this work identifies a new innate immunity role for parkin in ubiquitin-mediated autophagy of intracellular bacterial pathogens.

The crystal structure of BamA, the central component of the β-barrel assembly machinery (BAM) complex, from N. gonorrhoeae and H. ducreyi is determined; the structure consists of an interior cavity capped by extracellular loops, an exterior rim with a narrowed hydrophobic surface and a lateral opening of the barrel domain, providing insight into a possible route for the insertion of β-barrel membrane proteins into the bacterial outer membrane.

Here the authors present a human pluripotent stem cell-derived three-dimensional organoid culture system that is able to recapitulate several aspects of human brain development in addition to modelling the brain disorder microcephaly, which has been difficult to achieve using mouse models.

Reducing topoisomerase activity in mouse and human neurons is found to reduce the expression of long genes by impairing transcription elongation: among genes affected are numerous high-confidence candidates for autism spectrum disorder.