Cadherin-directed actin assembly: E-cadherin physically associates with the Arp2/3 complex to direct actin assembly in nascent adhesive contacts

Cadherin cell adhesion molecules are major determinants of tissue patterning which function in cooperation with the actin cytoskeleton [1-4]. In the context of stable adhesion [1], cadherin/catenin complexes are often envisaged to passively scaffold onto cortical actin filaments. However, cadherins also form dynamic adhesive contacts during wound healing and morphogenesis [2]. Here actin polymerization has been proposed to drive cell surfaces together [5], although F-actin reorganization also occurs as cell contacts mature [6]. The interaction between cadherins and actin is therefore likely to depend on the functional state of adhesion. We sought to analyze the relationship between cadherin homophilic binding and cytoskeletal activity during early cadherin adhesive contacts. Dissecting the specific effect of cadherin ligation alone on actin regulation is difficult in native cell-cell contacts, due to the range of juxtacrine signals that can arise when two cell surfaces adhere [7]. We therefore activated homophilic ligation using a specific functional recombinant protein. We report the first evidence that E-cadherin associates with the Arp2/3 complex actin nucleator and demonstrate that cadherin binding can exert an active, instructive influence on cells to mark sites for actin assembly at the cell surface.

Epidemiological significance of subterranean Aedes aegypti (Diptera : Culicidae) breeding sites to dengue virus infection in charters towers, 1993

The objective of this study was to determine the epidemiological significance of subterranean mosquito breeding sites to the 1993 outbreak of dengue fever (type 2) in the northern Queensland town of Charters Towers, Australia. In recent studies on subterranean mosquito breeding, containers such as wells and service manholes have been shown to be important breeding sites to Australia's only dengue vector, Aedes aegypti (L.). This study demonstrates a direct epidemiological association between subterranean breeding sites and dengue virus infection. The mean distance between residents seropositive for dengue 2 and the nearest subterranean container (113 m) was significantly less than for a randomly selected control (191 m), (F = 81.9; df = 1, 478; P < 0.001). Residents positive for dengue 2 antibodies was 2.47 (95% confidence interval 1.88-3.24) times higher for those living within 160 m of a well or service manhole, compared with those residing further away. These findings emphasize the importance of including subterranean water containers in Ae. aegypti surveillance and control programs.

Direct visualization of Ras proteins in spatially distinct cell surface microdomains

Localization of signaling complexes to specific micro-domains coordinates signal transduction at the plasma membrane. Using immunogold electron microscopy of plasma membrane sheets coupled with spatial point pattern analysis, we have visualized morphologically featureless microdomains including lipid rafts, in situ and at high resolution. We find that an inner-plasma membrane lipid raft marker displays cholesterol-dependent clustering in microdomains with a mean diameter of 44 nm that occupy 35% of the cell surface. Cross-linking an outer-leaflet raft protein results in the redistribution of inner leaflet rafts, but they retain their modular structure. Analysis of Ras microlocalization shows that inactive H-ras is distributed between lipid rafts and a cholesterol-independent micro-domain. Conversely, activated H-ras and K-ras reside predominantly in nonoverlapping, cholesterol-independent microdomains. Galectin-1 stabilizes the association of activated H-ras with these nonraft microdomains, whereas K-ras clustering is supported by farnesylation, but not geranylgeranylation. These results illustrate that the inner plasma membrane comprises a complex mosaic of discrete microdomains. Differential spatial localization within this framework can likely account for the distinct signal outputs from the highly homologous Ras proteins.

Valuing of firm's prior knowledge: A measure of knowledge distance

Knowledge, especially scientific and technological knowledge, grows according to knowledge trajectories and guideposts that make up the prior knowledge of an organization. We argue that these knowledge structures and their specific components lead to successful innovation. A firm's prior knowledge facilitates the absorption of new knowledge, thereby renewing a firm's systematic search, transfer and acquisition of knowledge and capabilities. In particular, the exponential growth in biotechnology is characterized by the convergence of disparate scientific and technological knowledge resources. This paper examines the shift from protein-based to DNA-based diagnostic technologies as an example, to quantify the value of a firm's prior knowledge using relative values of knowledge distance. The distance between core prior knowledge and the rate of transition from one knowledge system to another has been identified as a proxy for the value a firm's prior knowledge. The overall difficulty of transition from one technology paradigm to another is discussed. We argue this transition is possible when the knowledge distance is minimal and the transition process has a correspondingly high value of absorptive capacities. Our findings show knowledge distance is a determinant of the feasibility, continuity and capture of scientific and technological knowledge. Copyright © 2003 John Wiley & Sons, Ltd.

Making distance learning E.R.O.T.I.C.: Applying interpretation principles to distance learning

Distance learners are self-directed learners traditionally taught via study books, collections of readings, and exercises to test understanding of learning packages. Despite advances in e-Learning environments and computer-based teaching interfaces, distance learners still lack opportunities to participate in exercises and debates available to classroom learners, particularly through non-text based learning techniques. Effective distance teaching requires flexible learning opportunities. Using arguments developed in interpretation literature, we argue that effective distance learning must also be Entertaining, Relevant, Organised, Thematic, Involving and Creative—E.R.O.T.I.C. (after Ham, 1992). We discuss an experiment undertaken with distance learners at The University of Queensland Gatton Campus, where we initiated an E.R.O.T.I.C. external teaching package aimed at engaging distance learners but using multimedia, including but not limited to text-based learning tools. Student responses to non-text media were positive.

Fast, scalable master equation solution algorithms. III. Direct time propagation accelerated by a diffusion approximation preconditioned iterative solver

In this paper we propose a novel fast and linearly scalable method for solving master equations arising in the context of gas-phase reactive systems, based on an existent stiff ordinary differential equation integrator. The required solution of a linear system involving the Jacobian matrix is achieved using the GMRES iteration preconditioned using the diffusion approximation to the master equation. In this way we avoid the cubic scaling of traditional master equation solution methods and maintain the low temperature robustness of numerical integration. The method is tested using a master equation modelling the formation of propargyl from the reaction of singlet methylene with acetylene, proceeding through long lived isomerizing intermediates. (C) 2003 American Institute of Physics.

Direct electrochemistry of a bacterial sulfite dehydrogenase

Sulfite dehydrogenase from Starkeya novella is an alphabeta heterodimer comprising a 40.6 kDa subunit (containing the Mo cofactor) and a smaller 8.8 kDa heme c subunit. The enzyme catalyses the oxidation of sulfite to sulfate with the natural electron acceptor being cytochrome c(550). Its catalytic mechanism is thought to resemble that found in eukaryotic sulfite oxiclases. Using protein film voltammetry and redox potentiometry, we have identified both Mo- and heme-centered redox responses from the enzyme immobilized on a pyrolytic graphite working electrode: E-m,E-8 (Fe-III/II) +177 mV; E-m,E-8 (Mo-VI/V) +211 mV and E(m,)8 (Mo-V/IV) -118 mV vs NHE; Upon addition of sulfite to the electrochemical cell a steady-state voltammogram is observed and an apparent Michaelis constant (K-m) of 26(l) muM was determined for the enzyme immobilized on the working electrode surface, which is comparable with the value obtained from solution assays.

Effects of speaking rate on EMA-derived lingual kinematics: a preliminary investigation

Electromagnetic articulography (EMA) was used to investigate how tongue movement characteristics (i.e., velocity, acceleration, duration, distance) change with. or indeed affect, increased rates of speech. Eight young adult males repeated /ta/ and /ka/ syllables first at a moderate rate that had been modelled at three syllables per second, and then 'as fast as possible'. Distance travelled by the tongue appeared to be the principal lingual kinematic feature manipulated by the group of speakers in producing increased syllable repetition rates, with velocity found to increase, decrease or remain unchanged. Acceleration remained unchanged, except in the case of increased velocity. One participant formed an exception in terms of manipulating distance by exhibiting marginally increased lingual velocities rather than distance changes. This preliminary study serves to direct future EMA-based studies of speech rate control as to the speech tasks that should be employed and the possible underlying anatomical and acoustic bases or constraints that could possibly influence the kinematic strategies employed to increase speech rate.

Bridgehead arylation: A direct route to advanced intermediates for the synthesis of C-20 diterpene alkaloids

[GRAPHICS] Rapid access to the ABCE ring system of the C-20 diterpene alkaloids was achieved by silver(I)-promoted intramolecular Friedel-Crafts arylation of a functional group-specific 5-bromo-3-azabicyclo[3.3.1]nonane derivative.