LDL-receptor-related proteins in Wnt signal transduction

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex.     

Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.     

Subduction and collision processes in the Central Andes constrained by converted seismic phases

The Central Andes are the Earth's highest mountain belt formed by ocean-continent collision. Most of this uplift is thought to have occurred in the past 20 Myr, owing mainly to thickening of the continental crust, dominated by tectonic shortening. Here we use P-to-S (compressional-to-shear) converted teleseismic waves observed on several temporary networks in the Central Andes to image the deep structure associated with these tectonic processes. We find that the Moho (the Mohorovici? discontinuity--generally thought to separate crust from mantle) ranges from a depth of 75 km under the Altiplano plateau to 50 km beneath the 4-km-high Puna plateau. This relatively thin crust below such a high-elevation region indicates that thinning of the lithospheric mantle may have contributed to the uplift of the Puna plateau. We have also imaged the subducted crust of the Nazca oceanic plate down to 120 km depth, where it becomes invisible to converted teleseismic waves, probably owing to completion of the gabbro-eclogite transformation; this is direct evidence for the presence of kinetically delayed metamorphic reactions in subducting plates. Most of the intermediate-depth seismicity in the subducting plate stops at 120 km depth as well, suggesting a relation with this transformation. We see an intracrustal low-velocity zone, 10-20 km thick, below the entire Altiplano and Puna plateaux, which we interpret as a zone of continuing metamorphism and partial melting that decouples upper-crustal imbrication from lower-crustal thickening.     

The smallest known non-avian theropod dinosaur

Non-avian dinosaurs are mostly medium to large-sized animals, and to date all known mature specimens are larger than the most primitive bird, Archaeopteryx. Here we report on a new dromaeosaurid dinosaur, Microraptor zhaoianus gen. et sp. nov., from the Early Cretaceous Jiufotang Formation of Liaoning, China. This is the first mature non-avian dinosaur to be found that is smaller than Archaeopteryx, and it eliminates the size disparity between the earliest birds and their closest non-avian theropod relatives. The more bird-like teeth, the Rahonavis-like ischium and the small number of caudal vertebrae of Microraptor are unique among dromaeosaurids and improve our understanding of the morphological transition to birds. The nearly completely articulated foot shows features, such as distally positioned digit I, slender and recurved pedal claws, and elongated penultimate phalanges, that are comparable to those of arboreal birds. The discovery of these in non-avian theropods provides new insights for studying the palaeoecology of some bird-like theropod dinosaurs.     

Dichotomy of single-nucleotide polymorphism haplotypes in olfactory receptor genes and pseudogenes

Substantial efforts are focused on identifying single-nucleotide polymorphisms (SNPs) throughout the human genome, particularly in coding regions (cSNPs), for both linkage disequilibrium and association studies. Less attention, however, has been directed to the clarification of evolutionary processes that are responsible for the variability in nucleotide diversity among different regions of the genome. We report here the population sequence diversity of genomic segments within a 450-kb cluster of olfactory receptor (OR) genes on human chromosome 17. We found a dichotomy in the pattern of nucleotide diversity between OR pseudogenes and introns on the one hand and the closely interspersed intact genes on the other. We suggest that weak positive selection is responsible for the observed patterns of genetic variation. This is inferred from a lower ratio of polymorphism to divergence in genes compared with pseudogenes or introns, high non-synonymous substitution rates in OR genes, and a small but significant overall reduction in variability in the entire OR gene cluster compared with other genomic regions. The dichotomy among functionally different segments within a short genomic distance requires high recombination rates within this OR cluster. Our work demonstrates the impact of weak positive selection on human nucleotide diversity, and has implications for the evolution of the olfactory repertoire.     

Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor

The atrial natriuretic peptide (ANP) hormone is secreted by the heart in response to an increase in blood pressure. ANP exhibits several potent anti-hypertensive actions in the kidney, adrenal gland and vascular system. These actions are induced by hormone binding extracellularly to the ANP receptor, thereby activating its intracellular guanylyl cyclase domain for the production of cyclic GMP. Here we present the crystal structure of the glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A resolution. The monomer comprises two interconnected subdomains, each encompassing a central beta-sheet flanked by alpha-helices, and exhibits the type I periplasmic binding protein fold. Dimerization is mediated by the juxtaposition of four parallel helices, arranged two by two, which brings the two protruding carboxy termini into close relative proximity. From affinity labelling and mutagenesis studies, the ANP-binding site maps to the side of the dimer crevice and extends to near the dimer interface. A conserved chloride-binding site is located in the membrane distal domain, and we found that hormone binding is chloride dependent. These studies suggest mechanisms for hormone activation and the allostery of the ANP receptor.     

Stability analysis of the simplest Takagi-Sugeno fuzzy control system using circle criterion

A frequency-domain-based sufficient condition is derived to guarantee the globally asymptotic stability of the simplest Takagi-Sugeno (T-S) fuzzy control system by using the circle criterion. The analysis is performed in the frequency domain, and hence the condition is of great significance when the frequency-response method, which is widely used in the linear control theory and practice, is employed to synthesize the simplest T-S fuzzy controller. Besides, this sufficient condition is featured by a graphical interpretation, which makes the condition straightforward to be used. Comparisons are drawn between the performance of the simplest T-S fuzzy controller and that of the linear compensator. Two numerical examples are presented to demonstrate how this sufficient condition can be applied to both stable and unstable plants.     

中国明代弹道学史料的考辨与述评

对明代火器文献进行分析，认为学术界关于“中国古代弹道知识是由西方传来”之说值得商榷．中国弹道学知识的形成有其自身的特点，初步形成了能在一定程度上反映火器命中技术发展规律的弹道理论，在中国火器弹道科学思想史上占有重要地位．     

Photo Catalytic Oxidation of Alcohols in Water under Natural Weathering Conditions in the Presence of Bromo Source

1 Results The oxidation of alcohols into the corresponding carbonyl compound is one of the most important functional group transformation in organic synthesis[1]. Traditionally,such transformations have been performed with stoichiometric inorganic oxidant or other high valent metal oxidant[2]. Despite a variety of systems for the catalytic oxidation of alcohols have been developed,there is ongoing interest in the search for new efficient and environmental friendly oxidation system.To the best of our kno...