Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases

BACKGROUND: Trophoblast invasion is a temporally and spatially regulated scheme of events that can dictate pregnancy outcome. Evidence suggests that the potent mitogen epidermal growth factor (EGF) regulates cytotrophoblast (CTB) differentiation and invasion during early pregnancy. METHODS AND RESULTS: In the present study, the first trimester extravillous CTB cell line SGHPL-4 was used to investigate the signalling pathways involved in the motile component of EGF-mediated CTB migration/invasion. EGF induced the phosphorylation of the phosphatidylinositol 3-kinase (PI3-K)-dependent proteins, Akt and GSK-3β as well as both p42/44 MAPK and p38 mitogen-activated protein kinases (MAPK). EGF-stimulated motility was significantly reduced following the inhibition of PI3-K (P < 0.001), Akt (P < 0.01) and both p42/44 MAPK (P < 0.001) and p38 MAPKs (P < 0.001) but not the inhibition of GSK-3β. Further analysis indicated that the p38 MAPK inhibitor SB 203580 inhibited EGF-stimulated phosphorylation of Akt on serine 473, which may be responsible for the effect SB 203580 has on CTB motility. Although Akt activation leads to GSK-3β phosphorylation and the subsequent expression of β-catenin, activation of this pathway by 1-azakenpaullone was insufficient to stimulate the motile phenotype. CONCLUSION: We demonstrate a role for PI3-K, p42/44 MAPK and p38 MAPK in the stimulation of CTB cell motility by EGF, however activation of β-catenin alone was insufficient to stimulate cell motility.

Oriented vehicles travelling in spherical space

This paper tackles the path planning problem for oriented vehicles travelling in the non-Euclidean 3-Dimensional space; spherical space S3. For such problem, the orientation of the vehicle is naturally represented by orthonormal frame bundle; the rotation group SO(4). Orthonormal frame bundles of space forms coincide with their isometry groups and therefore the focus shifts to control systems defined on Lie groups. The oriented vehicles, in this case, are constrained to travel at constant speed in a forward direction and their angular velocities directly controlled. In this paper we identify controls that induce steady motions of these oriented vehicles and yield closed form parametric expressions for these motions. The paths these vehicles trace are defined explicitly in terms of the controls and therefore invariant with respect to the coordinate system used to describe the motion.

Designing persuasive third party applications for social networking services based on the 3D-RAB model

The use of social networks services for promoting business, teaching, learning, persuasion and spread of information continues to attract attention as most social networking services (SNSs) now allow third party applications to operate on their sites. In the field of persuasive technology, the ability of SNSs to build relationships among their users and create momentum and enthusiasm through rapid cycles also give it a greater advantage over other persuasive technology approaches. In this paper we discuss the 3-dimensional relationship between attitude and behavior (3D-RAB) model, and demonstrate how it can be used in designing third-party persuasive applications in SNSs by considering external factors which affects persuasive strategies.

A note on an integration by parts formula for the generators of uniform translations on configuration space

An integration by parts formula is derived for the first order differential operator corresponding to the action of translations on the space of locally finite simple configurations of infinitely many points on Rd. As reference measures, tempered grand canonical Gibbs measures are considered corresponding to a non-constant non-smooth intensity (one-body potential) and translation invariant potentials fulfilling the usual conditions. It is proven that such Gibbs measures fulfill the intuitive integration by parts formula if and only if the action of the translation is not broken for this particular measure. The latter is automatically fulfilled in the high temperature and low intensity regime.

Simulation of hurricane-type vortices in a general circulation model

A study of intense hurricane-type vortices in the ECMWF operational model is reported. These vortices develop around day 4 in the forecast and occur in the tropical belt in areas and at times where intense tropical cyclones normally occur. The frequency resembles that observed over most tropical regions with a pronounced maximum in the western North Pacific. The life time of the vortices and their 3-dimensional structure agree in some fundamental way with observations although, because of the resolution, the systems are less intense than the observed ones. The general large-scale conditions for active and inactive cyclone periods are discussed. The model cyclones are sensitive to the sea-surface temperature and do not develop with sea surface temperatures lower than 28–29°C. The dynamical conditions favouring cyclone development are characterized by intense large-scale divergence in the upper troposphere. Cyclogenesis appears to take place when these conditions are found outside the equatorial zone and over oceans where the water is sufficiently warm.

A maize bacterial artificial chromosome (BAC) library from the European flint inbred line F2

We report here the construction and characterisation of a BAC library from the maize flint inbred line F2, widely used in European maize breeding programs. The library contains 86,858 clones with an average insert size of approximately 90 kb, giving approximately 3.2-times genome coverage. High-efficiency BAC cloning was achieved through the use of a single size selection for the high-molecular-weight genomic DNA, and co-transformation of the ligation with yeast tRNA to optimise transformation efficiency. Characterisation of the library showed that less than 0.5% of the clones contained no inserts, while 5.52% of clones consisted of chloroplast DNA. The library was gridded onto 29 nylon filters in a double-spotted 8 × 8 array, and screened by hybridisation with a number of single-copy and gene-family probes. A 3-dimensional DNA pooling scheme was used to allow rapid PCR screening of the library based on primer pairs from simple sequence repeat (SSR) and expressed sequence tag (EST) markers. Positive clones were obtained in all hybridisation and PCR screens carried out so far. Six BAC clones, which hybridised to a portion of the cloned Rp1-D rust resistance gene, were further characterised and found to form contigs covering most of this complex resistance locus.

The vertical structure of oceanic Rossby waves: a comparison of high-resolution model data to theoretical vertical structures

Tests of the new Rossby wave theories that have been developed over the past decade to account for discrepancies between theoretical wave speeds and those observed by satellite altimeters have focused primarily on the surface signature of such waves. It appears, however, that the surface signature of the waves acts only as a rather weak constraint, and that information on the vertical structure of the waves is required to better discriminate between competing theories. Due to the lack of 3-D observations, this paper uses high-resolution model data to construct realistic vertical structures of Rossby waves and compares these to structures predicted by theory. The meridional velocity of a section at 24° S in the Atlantic Ocean is pre-processed using the Radon transform to select the dominant westward signal. Normalized profiles are then constructed using three complementary methods based respectively on: (1) averaging vertical profiles of velocity, (2) diagnosing the amplitude of the Radon transform of the westward propagating signal at different depths, and (3) EOF analysis. These profiles are compared to profiles calculated using four different Rossby wave theories: standard linear theory (SLT), SLT plus mean flow, SLT plus topographic effects, and theory including mean flow and topographic effects. Our results support the classical theoretical assumption that westward propagating signals have a well-defined vertical modal structure associated with a phase speed independent of depth, in contrast with the conclusions of a recent study using the same model but for different locations in the North Atlantic. The model structures are in general surface intensified, with a sign reversal at depth in some regions, notably occurring at shallower depths in the East Atlantic. SLT provides a good fit to the model structures in the top 300 m, but grossly overestimates the sign reversal at depth. The addition of mean flow slightly improves the latter issue, but is too surface intensified. SLT plus topography rectifies the overestimation of the sign reversal, but overestimates the amplitude of the structure for much of the layer above the sign reversal. Combining the effects of mean flow and topography provided the best fit for the mean model profiles, although small errors at the surface and mid-depths are carried over from the individual effects of mean flow and topography respectively. Across the section the best fitting theory varies between SLT plus topography and topography with mean flow, with, in general, SLT plus topography performing better in the east where the sign reversal is less pronounced. None of the theories could accurately reproduce the deeper sign reversals in the west. All theories performed badly at the boundaries. The generalization of this method to other latitudes, oceans, models and baroclinic modes would provide greater insight into the variability in the ocean, while better observational data would allow verification of the model findings.

Optimal steady motions for oriented vehicles

Motivated by the motion planning problem for oriented vehicles travelling in a 3-Dimensional space; Euclidean space E3, the sphere S3 and Hyperboloid H3. For such problems the orientation of the vehicle is naturally represented by an orthonormal frame over a point in the underlying manifold. The orthonormal frame bundles of the space forms R3,S3 and H3 correspond with their isometry groups and are the Euclidean group of motion SE(3), the rotation group SO(4) and the Lorentzian group SO(1; 3) respectively. Orthonormal frame bundles of space forms coincide with their isometry groups and therefore the focus shifts to left-invariant control systems defined on Lie groups. In this paper a method for integrating these systems is given where the controls are time-independent. For constant twist motions or helical motions, the corresponding curves g(t) 2 SE(3) are given in closed form by using the well known Rodrigues’ formula. However, this formula is only applicable to the Euclidean case. This paper gives a method for computing the non-Euclidean screw/helical motions in closed form. This involves decoupling the system into two lower dimensional systems using the double cover properties of Lie groups, then the lower dimensional systems are solved explicitly in closed form.

Solar causes of the long-term increase in geomagnetic activity

We analyze the causes of the century-long increase in geomagnetic activity, quantified by annual means of the aa index, using observations of interplanetary space, galactic cosmic rays, the ionosphere, and the auroral electrojet, made during the last three solar cycles. The effects of changes in ionospheric conductivity, the Earth's dipole tilt, and magnetic moment are shown to be small; only changes in near-Earth interplanetary space make a significant contribution to the long-term increase in activity. We study the effects of the interplanetary medium by applying dimensional analysis to generate the optimum solar wind-magnetosphere energy coupling function, having an unprecedentedly high correlation coefficient of 0.97. Analysis of the terms of the coupling function shows that the largest contributions to the drift in activity over solar cycles 20-22 originate from rises in the average interplanetary magnetic field (IMF) strength, solar wind concentration, and speed; average IMF orientation has grown somewhat less propitious for causing geomagnetic activity. The combination of these factors explains almost all of the 39% rise in aa observed over the last three solar cycles. Whereas the IMF strength varies approximately in phase with sunspot numbers, neither its orientation nor the solar wind density shows any coherent solar cycle variation. The solar wind speed peaks strongly in the declining phase of even-numbered cycles and can be identified as the chief cause of the phase shift between the sunspot numbers and the aa index. The rise in the IMF magnitude, the largest single contributor to the drift in geomagnetic activity, is shown to be caused by a rise in the solar coronal magnetic field, consistent with a rise in the coronal source field, modeled from photospheric observations, and an observed decay in cosmic ray fluxes.

Synthesis and NMR spectroscopic analysis of 3-nitro-pyranoside, 3-nitro-septanoside and 4-nitro-septanoside derivatives by condensation of the anion of nitromethane with glycoside

The utility of the nitroaldol reaction for accessing 3-nitro-pyranoside, 3-nitro-septanoside or 4-nitro-septanoside derivatives, by reaction of the anion of nitromethane with glycoside dialdehydes is demonstrated. Initially, the feasibility of using unprotected glucoside dialdehydes was probed for the synthesis of the septanoside products, but this affoided pyranoside rather than septanoside targets. Subsequent studies utilised protected glycoside dialdehydes within the methodology, which allowed entry into a range of 3-nitro or 4-nitro-septanosides in good yield NMR spectroscopic analysis allowed determination of the stereochemistry of each of the products thus afforded.

Monitoring and modelling the three-dimensional flow of water under drip irrigation

The interpretation of soil water dynamics under drip irrigation systems is relevant for crop production as well as on water use and management. In this study a three-dimensional representation of the flow of water under drip irrigation is presented. The work includes analysis of the water balance at point scale as well as area-average, exploring uncertainties in water balance estimations depending on the number of locations sampled. The water flow was monitored by detailed profile water content measurements before irrigation, after irrigation and 24 h later with a dense array of soil moisture access tubes radially distributed around selected drippers. The objective was to develop a methodology that could be used on selected occasions to obtain 'snap shots' of the detailed three-dimensional patterns of soil moisture. Such patterns are likely to be very complex, as spatial variability will be induced for a number of reasons, such as strong horizontal gradients in soil moisture, variations between individual sources in the amount of water applied and spatial variability is soil hydraulic properties. Results are compared with a widely used numerical model, Hydrus-2D. The observed dynamic of the water content distribution is in good agreement with model simulations, although some discrepancies concerning the horizontal distribution of the irrigation bulb are noted due to soil heterogeneity. (c) 2006 Elsevier B.V. All rights reserved.

Factors controlling the distribution of ozone in the West African lower troposphere during the AMMA (African Monsoon Multidisciplinary Analysis) wet season campaign

Ozone and its precursors were measured on board the Facility for Airborne Atmospheric Measurements (FAAM) BAe 146 Atmospheric Research Aircraft during the monsoon season 2006 as part of the African Monsoon Multidisciplinary Analysis (AMMA) campaign. One of the main features observed in the west African boundary layer is the increase of the ozone mixing ratios from 25 ppbv over the forested area (south of 12° N) up to 40 ppbv over the Sahelian area. We employ a two-dimensional (latitudinal versus vertical) meteorological model coupled with an O3-NOx-VOC chemistry scheme to simulate the distribution of trace gases over West Africa during the monsoon season and to analyse the processes involved in the establishment of such a gradient. Including an additional source of NO over the Sahelian region to account for NO emitted by soils we simulate a mean NOx concentration of 0.7 ppbv at 16° N versus 0.3 ppbv over the vegetated region further south in reasonable agreement with the observations. As a consequence, ozone is photochemically produced with a rate of 0.25 ppbv h−1 over the vegetated region whilst it reaches up to 0.75 ppbv h−1 at 16° N. We find that the modelled gradient is due to a combination of enhanced deposition to vegetation, which decreases the ozone levels by up to 11 pbbv, and the aforementioned enhanced photochemical production north of 12° N. The peroxy radicals required for this enhanced production in the north come from the oxidation of background CO and CH4 as well as from VOCs. Sensitivity studies reveal that both the background CH4 and partially oxidised VOCs, produced from the oxidation of isoprene emitted from the vegetation in the south, contribute around 5–6 ppbv to the ozone gradient. These results suggest that the northward transport of trace gases by the monsoon flux, especially during nighttime, can have a significant, though secondary, role in determining the ozone gradient in the boundary layer. Convection, anthropogenic emissions and NO produced from lightning do not contribute to the establishment of the discussed ozone gradient.

Proteornics analysis unravels the functional repertoire of coronavirus nonstructural protein 3

Severe acute respiratory syndrome (SARS) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. Proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. A complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. Mass spectrometry and kinase profiling techniques identified nearly 200 incorporated host and viral proteins. We used published interaction data to identify hubs of connectivity with potential significance for virion formation. Surprisingly, the hub with the most potential connections was not the viral M protein but the nonstructurall protein 3 (nsp3), which is one of the novel virion components identified by mass spectrometry. Based on new experimental data and a bioinformatics analysis across the Coronaviridae, we propose a higher-resolution functional domain architecture for nsp3 that determines the interaction capacity of this protein. Using recombinant protein domains expressed in Escherichia coli, we identified two additional RNA-binding domains of nsp3. One of these domains is located within the previously described SARS-unique domain, and there is a nucleic acid chaperone-like domain located immediately downstream of the papain-like proteinase domain. We also identified a novel cysteine-coordinated metal ion-binding domain. Analyses of interdomain interactions and provisional functional annotation of the remaining, so-far-uncharacterized domains are presented. Overall, the ensemble of data surveyed here paint a more complete picture of nsp3 as a conserved component of the viral protein processing machinery, which is intimately associated with viral RNA in its role as a virion component.

Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal epithelial cells using cysteine- and lysine-labelling two-dimensional difference gel electrophoresis

Differential protein expression analysis based on modification of selected amino acids with labelling reagents has become the major method of choice for quantitative proteomics. One such methodology, two-dimensional difference gel electrophoresis (2-D DIGE), uses a matched set of fluorescent N-hydroxysuccinimidyl (NHS) ester cyanine dyes to label lysine residues in different samples which can be run simultaneously on the same gels. Here we report the use of iodoacetylated cyanine (ICy) dyes (for labelling of cysteine thiols, for 2-D DIGE-based redox proteomics. Characterisation of ICy dye labelling in relation to its stoichiometry, sensitivity and specificity is described, as well as comparison of ICy dye with NHS-Cy dye labelling and several protein staining methods. We have optimised conditions for labelling of nonreduced, denatured samples and report increased sensitivity for a subset of thiol-containing proteins, allowing accurate monitoring of redox-dependent thiol modifications and expression changes. Cysteine labelling was then combined with lysine labelling in a multiplex 2-D DIGE proteomic study of redox-dependent and ErbB2-dependent changes in epithelial cells exposed to oxidative stress. This study identifies differentially modified proteins involved in cellular redox regulation, protein folding, proliferative suppression, glycolysis and cytoskeletal organisation, revealing the complexity of the response to oxidative stress and the impact that overexpression of ErbB2 has on this response.

Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal epithelial cells using cysteine- and lysine-labelling two-dimensional difference gel electrophoresis

Differential protein expression analysis based on modification of selected amino acids with labelling reagents has become the major method of choice for quantitative proteomics. One such methodology, two-dimensional difference gel electrophoresis (2-D DIGE), uses a matched set of fluorescent N-hydroxysuccinimidyl (NHS) ester cyanine dyes to label lysine residues in different samples which can be run simultaneously on the same gels. Here we report the use of iodoacetylated cyanine (ICy) dyes (for labelling of cysteine thiols, for 2-D DIGE-based redox proteomics. Characterisation of ICy dye labelling in relation to its stoichiometry, sensitivity and specificity is described, as well as comparison of ICy dye with NHS-Cy dye labelling and several protein staining methods. We have optimised conditions for labelling of nonreduced, denatured samples and report increased sensitivity for a subset of thiol-containing proteins, allowing accurate monitoring of redox-dependent thiol modifications and expression changes, Cysteine labelling was then combined with lysine labelling in a multiplex 2-D DIGE proteomic study of redox-dependent and ErbB2-dependent changes in epithelial cells exposed to oxidative stress. This study identifies differentially modified proteins involved in cellular redox regulation, protein folding, proliferative suppression, glycolysis and cytoskeletal organisation, revealing the complexity of the response to oxidative stress and the impact that overexpression of ErbB2 has on this response.