Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex

F-box proteins are members of a large family that regulates the cell cycle, the immune response, signalling cascades and developmental programmes by targeting proteins, such as cyclins, cyclin-dependent kinase inhibitors, IkappaBalpha and beta-catenin, for ubiquitination (reviewed in refs 1-3). F-box proteins are the substrate-recognition components of SCF (Skp1-Cullin-F-box protein) ubiquitin-protein ligases. They bind the SCF constant catalytic core by means of the F-box motif interacting with Skp1, and they bind substrates through their variable protein-protein interaction domains. The large number of F-box proteins is thought to allow ubiquitination of numerous, diverse substrates. Most organisms have several Skp1 family members, but the function of these Skp1 homologues and the rules of recognition between different F-box and Skp1 proteins remain unknown. Here we describe the crystal structure of the human F-box protein Skp2 bound to Skp1. Skp1 recruits the F-box protein through a bipartite interface involving both the F-box and the substrate-recognition domain. The structure raises the possibility that different Skp1 family members evolved to function with different subsets of F-box proteins, and suggests that the F-box protein may not only recruit substrate, but may also position it optimally for the ubiquitination reaction.     

Tracking an object through feature space

Visual attention allows an observer to select certain visual information for specialized processing. Selection is readily apparent in 'tracking' tasks where even with the eyes fixed, observers can track a target as it moves among identical distractor items. In such a case, a target is distinguished by its spatial trajectory. Here we show that one can keep track of a stationary item solely on the basis of its changing appearance--specified by its trajectory along colour, orientation, and spatial frequency dimensions--even when a distractor shares the same spatial location. This ability to track through feature space bears directly on competing theories of attention, that is, on whether attention can select locations in space, features such as colour or shape, or particular visual objects composed of constellations of visual features. Our results affirm, consistent with a growing body of psychophysical and neurophysiological evidence, that attention can indeed select specific visual objects. Furthermore, feature-space tracking extends the definition of visual object to include not only items with well defined spatio-temporal trajectories, but also those with well defined featuro-temporal trajectories.     

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...     

Mediation of virion penetration into vascular cells by association of basic fibroblast growth factor with herpes simplex virus type 1

Herpes simplex virus type-1 (HSV-1) is a ubiquitous pathogen that is associated with considerable morbidity in the general population. Although it is known that the virion uses a basic fibroblast growth factor (FGF) receptor to penetrate vascular cells, it is not known how the viral particle recognizes and binds to this cell surface protein. Here we report that an immunoreactive basic FGF-like protein is associated with the viral particle and that this association appears responsible for viral uptake. Accordingly, HSV-1 infection of Swiss 3T3 cells stimulates the tyrosine phosphorylation of the specific substrate that characterizes the initial cellular response to basic FGF. Antibodies to basic FGF prevent this phosphorylation and inhibit HSV-1 uptake. Because no basic FGF sequence is found in the HSV-1 genome, a model for the infection for some target cells is presented whereby the viral particle uses host cell-derived basic FGF to ensure subsequent infectivity of newly replicated virus.     

Interpretation of Fashion Change through the Thoughts of Hong Kong Young Consumers

Fashion changes frequently, on monthly, seasonal to yearly basis. In different periods of time, people tried to use different theories to explain the concept of fashion change. Traditional views including trickle down theory, collective selection theory, mass market theory and subculture leadership theory. From the viewpoint of contemporary thoughts, symbolic interactionist theory of fashion and the power of the fashion industry were discussed and used to examine fashion images prevailing in Hong Kong. Hong Kong young consumers were selected as study samples. Focus group interviews and questionnaire survey were used as qualitative and quantitative method. Results shows that to accept fashion change, status (working or studying) had influence in interpreting fashion images. In addition, male and female students had different opinion on selected statements of the symbolic interactionist theory of fashion but no difference was found between working subjects. Marketing implications are discussed with refere     

Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure.

Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA.     

A family of mammalian Na+-dependent L-ascorbic acid transporters.

Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs.