Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling

The gut microbiota is a complex ecosystem that has coevolved with host physiology. Colonization of germ-free (GF) mice with a microbiota promotes increased vessel density in the small intestine, but little is known about the mechanisms involved. Tissue factor (TF) is the membrane receptor that initiates the extrinsic coagulation pathway, and it promotes developmental and tumour angiogenesis. Here we show that the gut microbiota promotes TF glycosylation associated with localization of TF on the cell surface, the activation of coagulation proteases, and phosphorylation of the TF cytoplasmic domain in the small intestine. Anti-TF treatment of colonized GF mice decreased microbiota-induced vascular remodelling and expression of the proangiogenic factor angiopoietin-1 (Ang-1) in the small intestine. Mice with a genetic deletion of the TF cytoplasmic domain or with hypomorphic TF (F3) alleles had a decreased intestinal vessel density. Coagulation proteases downstream of TF activate protease-activated receptor (PAR) signalling implicated in angiogenesis. Vessel density and phosphorylation of the cytoplasmic domain of TF were decreased in small intestine from PAR1-deficient (F2r(-/-)) but not PAR2-deficient (F2rl1(-/-)) mice, and inhibition of thrombin showed that thrombin-PAR1 signalling was upstream of TF phosphorylation. Thus, the microbiota-induced extravascular TF-PAR1 signalling loop is a novel pathway that may be modulated to influence vascular remodelling in the small intestine.     

Surface-enhanced Raman scattering on dual-layer metallic grating structures

Dual-layer Metallic grating (DMG) structures as surface-enhanced Raman scattering (SERS) substrates are studied using ben-zenethiol as the probe analyte. The DMG structure consists of a SiO₂ grating and 100-nm-thick gold coating layers. An enhancement factor of 10⁵ is achieved by optimizing the SiO₂ grating height within the range from 165 to 550 nm. The enhancement factor dependence on the SiO₂ grating height is due to the surface plasmon excitation, which is dependent on the polarization of the incident light, and confirmed by finite difference time domain simulations. This study demonstrates the advantages of high uniformity, reproducibility and sensitivity in the DMG structures for SERS applications.     

拟南芥中一个经典阿拉伯半乳糖蛋白的亚细胞定位

为确定拟南芥中一个经典阿拉伯半乳糖蛋白(arabinogalactan-protein,AGP)的亚细胞定位,克隆了这个基因的编码区,与绿色荧光蛋白(GFP)基因构建融合表达载体,经农杆菌介导转化烟草BY-2悬浮细胞.利用激光扫描共聚焦显微镜,在稳定转化的BY-2细胞表面观察到绿色荧光.研究结果表明,此AGP分布在细胞膜表面.     

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades.     

Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis

Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated α-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme from a non-enzymatic ancestor over a defined period of plant evolution.     

A classifying procedure for signalling turning points

A Hidden Markov Model (HMM) is used to classify an out‐of‐sample observation vector into either of two regimes. This leads to a procedure for making probability forecasts for changes of regimes in a time series, i.e. for turning points. Instead of estimating past turning points using maximum likelihood, the model is estimated with respect to known past regimes. This makes it possible to perform feature extraction and estimation for different forecasting horizons. The inference aspect is emphasized by including a penalty for a wrong decision in the cost function. The method, here called a ‘Markov Bayesian Classifier (MBC)’, is tested by forecasting turning points in the Swedish and US economies, using leading data. Clear and early turning point signals are obtained, contrasting favourably with earlier HMM studies. Some theoretical arguments for this are given. Copyright © 2004 John Wiley & Sons, Ltd.     

Type I iodothyronine deiodinase is a selenocysteine-containing enzyme.

Although thyroxine (3,5,3',5'-tetraiodothyronine, T4) is the principal secretory product of the vertebrate thyroid, its essential metabolic and developmental effects are all mediated by 3,5,3'-triiodothyronine (T3), which is produced from the prohormone by 5'-deiodination. The type-I iodothyronine deiodinase, a thiol-requiring propylthiouracil-sensitive oxidoreductase, is found mainly in liver and kidney and provides most of the circulating T3(1) but so far this enzyme has not been purified. Using expression cloning in the Xenopus oocyte, we have isolated a 2.1-kilobase complementary DNA for this deiodinase from a rat liver cDNA library. The kinetic properties of the protein expressed in transient assay systems, the tissue distribution of the messenger RNA, and its changes with thyroid status, all confirm its identity. We find that the mRNA for this enzyme contains a UGA codon for selenocysteine which is necessary for maximal enzyme activity. This explains why conversion of T4 to T3 is impaired in experimental selenium deficiency and identifies an essential role for this trace element in thyroid hormone action.     

An assessment of the economic value of non-linear foreign exchange rate forecasts

Recent research suggests that non-linear methods cannot improve the point forecasts of high-frequency exchange rates. These studies have been using standard forecasting criteria such as smallest mean squared error (MSE) and smallest mean absolute error (MAE). It is, however, premature to conclude from this evidence that non-linear forecasts of high-frequency financial returns are economically or statistically insignificant. We prove a proposition which implies that the standard forecasting criteria are not necessarily particularly suited for assessment of the economic value of predictions of non-linear processes where the predicted value and the prediction error may not be independently distributed. Adopting a simple non-linear forecasting procedure to 15 daily exchange rate series we find that although, when compared to simple random walk forecasts, all the non-linear forecasts give a higher MSE and MAE, when applied in a simple trading strategy these forecasts result in a higher mean return. It is also shown that the ranking of portfolio payoffs based on forecasts from a random walk, and linear and non-linear models, is closely related to a non-parametric test of market timing.