Research articles

A significant effect of anthropogenic activities has already been detected in observed trends in temperature and mean precipitation. But so far, no study has formally identified such a human fingerprint on extreme precipitation — an increase in which is one of the central theoretical expectations for a warming climate. This study compares observations and simulations and detects a statistically significant effect of increased greenhouse gases on observed increases in extreme precipitation events over much of the Northern Hemisphere land area.

The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies with star formation rates at the level of a few hundred solar masses per year. These faint submillimetre galaxies are challenging to study individually, but their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. This study reports excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500 micrometres. It is found that submillimetre galaxies are located in dark matter haloes with a minimum mass of log₁₀[M_min/solar mass]=11.5^+0.7_-0.2 at 350° micrometres.

In a mouse model of Erbb2-driven mammary tumours, this study finds a role for RANKL in the formation of lung metastases. RANKL is produced by regulatory T cells infiltrating the primary tumours and acts via its receptor RANK expressed on the cancer cells. Targeting RANKL may therefore prove useful in reducing breast cancer metastases.

This study focuses on developing mouse skin where mitotic basal progenitor cells switch from symmetric divisions to asymmetric division concomitant with stratification. Using a novel technical approach, the genetic pathway regulating spindle orientation is dissected, providing the first direct evidence that the proteins governing spindle orientation (LGN, NuMA and Dctn1) promote asymmetric cell divisions regulated by Notch signalling in mammalian cells in vivo.

Human emissions of greenhouse gasses — and related warming — have been shown to be an influence on global and regional warming and on broad-scale precipitation changes. But so far, assessing the human imprint on specific weather events has proven difficult. Now, publicly contributed climate simulations are used to show that increased greenhouse gas emissions substantially increased the risk of flood occurrence during the catastrophic 2000 England and Wales floods.

Activating AMPK or inactivating calcineurin slows ageing in worms and increases their lifespan. Here it is shown that inhibition of CRTC-1 is required for these life-extending effects. CRTC-1 is the only worm member in the family of CREB-regulated transcriptional co-activators, or CRTCs, and, like the mammalian family members, CRTC-1 interacts with a worm homologue of the CREB transcription factor (CRH-1). Eliminating crtc-1 increases lifespan in a crh-1-dependent manner, as does elimination of crh-1 alone. Downregulation of components in the CRTC/CREB pathway has previously been shown to confer health benefits to mice, complementing their lifespan effects in worms.

Embryonic stem cells are typically driven to adopt a neural fate in response to inductive signals originating from the environment. However, little is known regarding the downstream molecular mechanisms operating intracellularly to induce this transformation and differentiation. Here, the zinc-finger nuclear protein Zfp521 is demonstrated to be necessary and sufficient to force a neural fate, providing evidence for a cell-intrinsic factor important in transitioning multipotent ES cells to a neural fate.

Gene expression fluctuates in concert with the day/night cycle, and this results in differential behaviours throughout the day. These changes in expression have been studied at the transcriptional and post-translational levels. Here, another type of circadian-influenced regulation that occurs at the post-transcriptional level is defined. The twenty-four (TYF) protein associates with the mRNA of the clock protein PER, enhancing its translation.

Activation of inflammatory gene expression by toll-like receptor (TLR) signalling pathways involves the removal of gene repression complexes such as NCoR. Here, coronin 2A, a component of the NCoR complex, is shown to mediate TLR-induced NCoR turnover and de-repression of inflammatory genes by a mechanism involving interaction with oligomeric nuclear actin.

This study shows, via a mouse model of intestinal cancer, that in the absence of CKIα, the loss of p53 dramatically enhances tumour progression and metastasis. p53 is shown to normally limit cancer cell invasion via the regulation of p21 and a set of invasion genes that include Prox1. This study adds important insights to the emerging picture that during tumour development the p53 tumour suppressor gene not only controls cell death and proliferation but also metastasis.

Here, the X-ray crystal structure of TrkH is solved, a protein that mediates potassium uptake in Vibrio parahaemolyticus, a bacterium. The selectivity filter of the ion transporter is very similar to what is seen in (much simpler) potassium ion channels, but it is significantly shorter. Biochemical studies were performed to explore the molecular basis of K⁺ selectivity, and it is believed that a novel gating mechanism is involved.

The retina is a laminated structure made up of several different cellular subtypes that assemble precise connections between them. This study sheds new light on the molecular mechanisms governing the development of these specific circuits. Transmembrane molecules typically most active as repulsive signals during axonal guidance exhibit specific expression patterns within the retina, allowing for the connectivity between cell types to occur properly. Mutant mice lacking specific isoforms of these semaphorin or plexin molecular families displayed significant defects in the retinal circuitry. Thus, repulsive cues present on the neuronal processes themselves drive proper wiring between lamina within the retina.

In geometrically frustrated materials there is an intrinsic incompatibility between fundamental interaction rules and the underlying lattice geometry, which leads to exotic material behaviour. So far, geometric frustration has been reported for a range of magnetic materials but not yet in ferroelectrics, which would be of significant fundamental interest. This study reports computational results that show that geometric frustration can be induced in ferroelectrics with compositional grading. The findings reveal unusual ordered phases, allowing new microscopic insights in the phenomenon of geometric frustration.

Here it is shown that chiral dithiophosphoric acids can catalyse the intramolecular hydroamination and hydroarylation of dienes and allenes to generate heterocyclic products in exceptional yield and enantiomeric excess. A mechanistic hypothesis is presented that involves the addition of the acid catalyst to the diene, followed by S_N2′ displacement of the resulting dithiophosphate intermediate, and mass spectroscopic and deuterium labelling studies support the proposed mechanism.

The Antarctic Peninsula is currently one of the fastest-warming locations on Earth, but its long-term variability has remained unclear. This study uses TEX₈₆ sea surface temperature proxy evidence to show that a long-term cooling of about 3–4 °C occurred in waters near the tip of the Antarctic Peninsula over the past 12,000 years, consistent with orbitally controlled changes in insolation. Shorter-term variability in temperature at the Antarctic Peninsula appears to have been strongly influenced by the position of westerly winds. The present influence of the El Niño/Southern Oscillation system on the Antarctic Peninsula may have arisen only during the late Holocene.

In a significant step forward in complexity and capability for bottom-up assembly of nanoelectronic circuits, this study demonstrates scalable and programmable logic tiles based on semiconductor nanowire transistor arrays. The same logic tile, consisting 496 configurable transistor nodes in an area of about 960 μm², could be programmed and operated as, among other functions, a full-adder, full-subtractor and multiplexer. The promise is that these logic tiles can be cascaded to realize fully integrated nanoprocessors with computing, memory and addressing capabilities.

Here it is shown that telomere dysfunction drives metabolic and mitochondrial compromise. Mice with dysfunctional telomeres activate p53, which in turn represses PGC-1α and PGC-1β, master regulators of metabolic and mitochondrial processes. This results in reduced mitochondrial mass, mitochondrial dysfunction and reduced ATP generation, impaired gluconeogenesis, cariomyopathy and increased reactive oxygen species. This telomere–p53–PGC pathway shows how telomere dysfunction may compromise organ function and contribute to age-related disorders.

The APC/C is a large multiprotein complex that functions as an E3 ubiquitin ligase to regulate the cell cycle. Here, the entire APC/C complex is reconstituted, and in combination with structural studies a pseudo-atomic model for 70% of the complex is provided. These results contribute towards a molecular understanding of the roles of individual subunits in APC/C assembly and their interactions with co-activators, substrates and regulatory proteins.

The vitamin A metabolite retinoic acid is shown to act in conjunction with IL-15 to induce IL-12p70 production by intestinal dendritic cells, thereby promoting an inflammatory T-cell response to dietary antigens. The mechanism may underlie coeliac disease pathogenesis.