Flushing submarine canyons

The continental slope is a steep, narrow fringe separating the coastal zone from the deep ocean. During low sea-level stands, slides and dense, sediment-laden flows erode the outer continental shelf and the continental slope, leading to the formation of submarine canyons that funnel large volumes of sediment and organic matter from shallow regions to the deep ocean(1). During high sea-level stands, such as at present, these canyons still experience occasional sediment gravity flows(2-5), which are usually thought to be triggered by sediment failure or river flooding. Here we present observations from a submarine canyon on the Gulf of Lions margin, in the northwest Mediterranean Sea, that demonstrate that these flows can also be triggered by dense shelf water cascading (DSWC)-a type of current that is driven solely by seawater density contrast. Our results show that DSWC can transport large amounts of water and sediment, reshape submarine canyon floors and rapidly affect the deep-sea environment. This cascading is seasonal, resulting from the formation of dense water by cooling and/or evaporation, and occurs on both high- and low-latitude continental margins(6-8). DSWC may therefore transport large amounts of sediment and organic matter to the deep ocean. Furthermore, changes in the frequency and intensity of DSWC driven by future climate change may have a significant impact on the supply of organic matter to deep-sea ecosystems and on the amount of carbon stored on continental margins and in ocean basins.     

Quantum phase transition in a single-molecule quantum dot

Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many-particle physical system is forced to evolve continuously between two distinct, competing ground states. This phenomenon, often related to a zero-temperature magnetic phase transition, is believed to govern many of the fascinating properties of strongly correlated systems such as heavy-fermion compounds or high-temperature superconductors. In contrast to bulk materials with very complex electronic structures, artificial nanoscale devices could offer a new and simpler means of understanding quantum phase transitions. Here we demonstrate this possibility in a single-molecule quantum dot, where a gate voltage induces a crossing of two different types of electron spin state (singlet and triplet) at zero magnetic field. The quantum dot is operated in the Kondo regime, where the electron spin on the quantum dot is partially screened by metallic electrodes. This strong electronic coupling between the quantum dot and the metallic contacts provides the strong electron correlations necessary to observe quantum critical behaviour. The quantum magnetic phase transition between two different Kondo regimes is achieved by tuning gate voltages and is fundamentally different from previously observed Kondo transitions in semiconductor and nanotube quantum dots. Our work may offer new directions in terms of control and tunability for molecular spintronics.     

Variation in FTO contributes to childhood obesity and severe adult obesity

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.     

Surface display of a single-domain antibody library on Gram-positive bacteria

Combinatorial protein engineering for selection of proteins with novel functions, such as enzymes and affinity reagents, is an important tool in biotechnology, drug discovery, and other biochemical fields. Bacterial display is an emerging technology for isolation of new affinity proteins from such combinatorial libraries. Cells have certain properties that are attractive for directed evolution purposes, in particular the option to use quantitative flow-cytometric cell sorting for selection of binders. Here, an immune library of around 10⁷ camelid single-domain antibody fragments (Nanobodies) was displayed on both the Gram-positive bacterium Staphylococcus carnosus and on phage. As demonstrated for the first time, the antibody repertoire was found to be well expressed on the bacterial surface and flow-cytometric sorting yielded a number of Nanobodies with subnanomolar affinity for the target protein, green fluorescent protein (GFP). Interestingly, the staphylococcal output repertoire and the binders from the phage display selection contained two slightly different sets of clones, containing both unique as well as several similar variants. All of the Nanobodies from the staphylococcal selection were also shown to enhance the fluorescence of GFP upon binding, potentially due to the fluorescence-based sorting principle. Our study highlights the impact of the chosen display technology on the variety of selected binders and thus the value of having alternative methods available, and demonstrates in addition that the staphylococcal system is suitable for generation of high-affinity antibody fragments.     

Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells

The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined, in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages. In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424, through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which led to experimentally inaccessible predictions on p70S6K phosphorylation rate.     

峭壁之国的公路之旅

<正>浪花拍击着岩石,这里是爱尔兰最南端的米曾角。海角通过吊桥与海岸相连,此处有闻名全国的灯塔。非常狭窄的爱尔兰公路两边是树篱和斜坡,野生大蒜、杜鹃花、吊钟海棠如此旺盛地生长着。我们常常要在崎岖无比的道路上刹车,避免和迎面而来的车相撞。随后,当车子轻轻地刮到了建筑物的铁制装饰时,引得路边山楂树枝叶窸窣作响。街边偶遇的爱尔兰人友好地打着招呼,这是表