Snapshots of nuclear pore complexes in action captured by cryo-electron tomography

Nuclear pore complexes reside in the nuclear envelope of eukaryotic cells and mediate the nucleocytoplasmic exchange of macromolecules. Traffic is regulated by mobile transport receptors that target their cargo to the central translocation channel, where phenylalanine-glycine-rich repeats serve as binding sites. The structural analysis of the nuclear pore is a formidable challenge given its size, its location in a membranous environment and its dynamic nature. Here we have used cryo-electron tomography to study the structure of nuclear pore complexes in their functional environment, that is, in intact nuclei of Dictyostelium discoideum. A new image-processing strategy compensating for deviations of the asymmetric units (protomers) from a perfect eight-fold symmetry enabled us to refine the structure and to identify new features. Furthermore, the superposition of a large number of tomograms taken in the presence of cargo, which was rendered visible by gold nanoparticles, has yielded a map outlining the trajectories of import cargo. Finally, we have performed single-molecule Monte Carlo simulations of nuclear import to interpret the experimentally observed cargo distribution in the light of existing models for nuclear import.     

Electrodeposition of Al from a 1-butylpyrrolidine-AlCl3 ionic liquid

The addition of 1-butylpyrrolidine to AlCl_3 results in the formation of an electrolyte that is suited to Al deposition.The feasibility of electrodepositing Al from the synthesized electrolyte was investigated.Several compositions of AlCl_3 and 1-butylpyrrolidine were prepared for this purpose.These mixtures show a different phase behavior at various compositions of AlCl_3 and 1-butylpyrrolidine.IR,Raman and NMR spectroscopy were employed to characterize the synthesized liquids.Among the prepared compositions,1:1.2 mol ratio of 1-butylpyrrolidine:AlCl_3 and the upper phase of 1:1.3 mol ratio of 1-butylpyrrolidine:AlCl_3 were found to be suitable for Al electrodeposition at room temperature(RT).Uniform and thick( mm thick) layers of Al were obtained on copper at RT.Al deposition occured from the cationic species of AlCl_3 xLty(where x r 2,y ? 1–2,and L ? 1-butylpyrrolidine) in this electrolyte.This behavior is contrary to the well investigated classic AlCl_3 based ionic liquids,where the deposition of Al occurs mainly from anionic Al2 Cl 7ions.     

A genome-wide association study of metabolic traits in human urine

We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria.     

Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia

The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. Here, we identify a locus for an autosomal dominant form of brachyolmia on chromosome 12q24.1-12q24.2. Among the genes in the genetic interval, we selected TRPV4, which encodes a calcium permeable cation channel of the transient receptor potential (TRP) vanilloid family, as a candidate gene because of its cartilage-selective gene expression pattern. In two families with the phenotype, we identified point mutations in TRPV4 that encoded R616Q and V620I substitutions, respectively. Patch clamp studies of transfected HEK cells showed that both mutations resulted in a dramatic gain of function characterized by increased constitutive activity and elevated channel activation by either mechano-stimulation or agonist stimulation by arachidonic acid or the TRPV4-specific agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD). This study thus defines a previously unknown mechanism, activation of a calcium-permeable TRP ion channel, in skeletal dysplasia pathogenesis.     

A TAS1R receptor-based explanation of sweet 'water-taste'

'Water-tastes' are gustatory after-impressions elicited by water following the removal of a chemical solution from the mouth, akin to colour after-images appearing on 'white' paper after fixation on coloured images. Unlike colour after-images, gustatory after-effects are poorly understood. One theory posits that 'water-tastes' are adaptation phenomena, in which adaptation to one taste solution causes the water presented subsequently to act as a taste stimulus. An alternative hypothesis is that removal of the stimulus upon rinsing generates a receptor-based, positive, off-response in taste-receptor cells, ultimately inducing a gustatory perception. Here we show that a sweet 'water-taste' is elicited when sweet-taste inhibitors are rinsed away. Responses of cultured cells expressing the human sweetener receptor directly parallel the psychophysical responses-water rinses remove the inhibitor from the heteromeric sweetener receptor TAS1R2-TAS1R3, which activates cells and results in the perception of strong sweetness from pure water. This 'rebound' activity occurs when equilibrium forces on the two-state allosteric sweet receptors result in their coordinated shift to the activated state upon being released from inhibition by rinsing.     

DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response

Matter structured on a length scale comparable to or smaller than the wavelength of light can exhibit unusual optical properties. Particularly promising components for such materials are metal nanostructures, where structural alterations provide a straightforward means of tailoring their surface plasmon resonances and hence their interaction with light. But the top-down fabrication of plasmonic materials with controlled optical responses in the visible spectral range remains challenging, because lithographic methods are limited in resolution and in their ability to generate genuinely three-dimensional architectures. Molecular self-assembly provides an alternative bottom-up fabrication route not restricted by these limitations, and DNA- and peptide-directed assembly have proved to be viable methods for the controlled arrangement of metal nanoparticles in complex and also chiral geometries. Here we show that DNA origami enables the high-yield production of plasmonic structures that contain nanoparticles arranged in nanometre-scale helices. We find, in agreement with theoretical predictions, that the structures in solution exhibit defined circular dichroism and optical rotatory dispersion effects at visible wavelengths that originate from the collective plasmon-plasmon interactions of the nanoparticles positioned with an accuracy better than two nanometres. Circular dichroism effects in the visible part of the spectrum have been achieved by exploiting the chiral morphology of organic molecules and the plasmonic properties of nanoparticles, or even without precise control over the spatial configuration of the nanoparticles. In contrast, the optical response of our nanoparticle assemblies is rationally designed and tunable in handedness, colour and intensity-in accordance with our theoretical model.     

Second‐Generation Prediction Markets for Information Aggregation: A Comparison of Payoff Mechanisms

Initial applications of prediction markets (PMs) indicate that they provide good forecasting instruments in many settings, such as elections, the box office, or product sales. One particular characteristic of these ‘first‐generation’ (G1) PMs is that they link the payoff value of a stock's share to the outcome of an event. Recently, ‘second‐generation’ (G2) PMs have introduced alternative mechanisms to determine payoff values which allow them to be used as preference markets for determining preferences for product concepts or as idea markets for generating and evaluating new product ideas. Three different G2 payoff mechanisms appear in the existing literature, but they have never been compared. This study conceptually and empirically compares the forecasting accuracy of the three G2 payoff mechanisms and investigates their influence on participants' trading behavior. We find that G2 payoff mechanisms perform almost as well as their G1 counterpart, and trading behavior is very similar in both markets (i.e. trading prices and trading volume), except during the very last trading hours of the market. These results indicate that G2 PMs are valid instruments and support their applicability shown in previous studies for developing new product ideas or evaluating new product concepts. Copyright © 2011 John Wiley & Sons, Ltd.     

Anaerobic oxidation of short-chain hydrocarbons by marine sulphate-reducing bacteria

The short-chain hydrocarbons ethane, propane and butane are constituents of natural gas. They are usually assumed to be of thermochemical origin, but biological formation of ethane and propane has been also observed. Microbial utilization of short-chain hydrocarbons has been shown in some aerobic species but not in anaerobic species of bacteria. On the other hand, anaerobic utilization of short-chain hydrocarbons would in principle be expected because various anaerobic bacteria grow with higher homologues (> or =C(6)). Indeed, chemical analyses of hydrocarbon-rich habitats with limited or no access of oxygen indicated in situ biodegradation of short-chain hydrocarbons. Here we report the enrichment of sulphate-reducing bacteria (SRB) with such capacity from marine hydrocarbon seep areas. Propane or n-butane as the sole growth substrate led to sediment-free sulphate-reducing enrichment cultures growing at 12, 28 or 60 degrees C. With ethane, a slower enrichment with residual sediment was obtained at 12 degrees C. Isolation experiments resulted in a mesophilic pure culture (strain BuS5) that used only propane and n-butane (methane, isobutane, alcohols or carboxylic acids did not support growth). Complete hydrocarbon oxidation to CO2 and the preferential oxidation of 12C-enriched alkanes were observed with strain BuS5 and other cultures. Metabolites of propane included iso- and n-propylsuccinate, indicating a subterminal as well as an unprecedented terminal alkane activation with involvement of fumarate. According to 16S ribosomal RNA analyses, strain BuS5 affiliates with Desulfosarcina/Desulfococcus, a cluster of widespread marine SRB. An enrichment culture with propane growing at 60 degrees C was dominated by Desulfotomaculum-like SRB. Our results suggest that diverse SRB are able to thrive in seep areas and gas reservoirs on propane and butane, thus altering the gas composition and contributing to sulphide production.