Role of the two-component regulator CpxAR in the virulence of Salmonella entetica serotype typhimurium

The CpxAR (Cpx) two-component regulator controls the expression of genes in response to a variety of environmental cues. The Cpx regulator has been implicated in the virulence of several gram-negative pathogens, although a role for Cpx in vivo has not been demonstrated directly. Here we investigate whether positive or negative control of gene expression by Cpx is important for the pathogenesis of Salmonella enterica serotype Typhimurium. The Cpx signal pathway in serotype Typhimurium was disrupted by insertional inactivation of the cpxA and cpxR genes. We also constitutively activated the Cpx pathway by making an internal in-frame deletion in cpxA (a cpxA* mutation). Activation of the Cpx pathway inhibited induction of the envelope stress response pathway controlled by the alternative sigma factor sigma(E) (encoded by rpoE). Conversely, the Cpx pathway was highly up-regulated (>40-fold) in a serotype Typhimurium rpoE mutant. The cpxA* mutation, but not the cpxA or the cpxR mutation, significantly reduced the capacity of serotype Typhimurium to adhere to and invade eucaryotic cells, although intracellular replication was not affected. The cpxA and cpxA* mutations significantly impaired the ability of serotype Typhimurium to grow in vivo in mice. To our knowledge, this is the first demonstration that the Cpx system is important for a bacterial pathogen in vivo.

Incorporation of a physically based melt pond scheme into the sea ice component of a climate model

The extent and thickness of the Arctic sea ice cover has decreased dramatically in the past few decades with minima in sea ice extent in September 2005 and 2007. These minima have not been predicted in the IPCC AR4 report, suggesting that the sea ice component of climate models should more realistically represent the processes controlling the sea ice mass balance. One of the processes poorly represented in sea ice models is the formation and evolution of melt ponds. Melt ponds accumulate on the surface of sea ice from snow and sea ice melt and their presence reduces the albedo of the ice cover, leading to further melt. Toward the end of the melt season, melt ponds cover up to 50% of the sea ice surface. We have developed a melt pond evolution theory. Here, we have incorporated this melt pond theory into the Los Alamos CICE sea ice model, which has required us to include the refreezing of melt ponds. We present results showing that the presence, or otherwise, of a representation of melt ponds has a significant effect on the predicted sea ice thickness and extent. We also present a sensitivity study to uncertainty in the sea ice permeability, number of thickness categories in the model representation, meltwater redistribution scheme, and pond albedo. We conclude with a recommendation that our melt pond scheme is included in sea ice models, and the number of thickness categories should be increased and concentrated at lower thicknesses.

One-pot three component reaction involving cyclohexyl isocyanide for the synthesis of furo[3,4-b]chromenes

On stirring an equimolar mixture of 4-oxo-4H-chromene-3-carbaldehyde, ninhydrin and cyclohexyl isocyanide in CH(2)Cl(2)-MeOH (7: 1) at room temperature produces 3-cyclohexylimino-1-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-1,3-dihydro-9H-furo[3,4-b]chromen-9-one which on hydrolysis produces 1-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-1H-furo[3,4-b]chromene-3,9-dione. The structure of the latter compound was confirmed by single crystal X-ray diffraction

Roll of the rhythmic component in the proactive control of a human hand

In terms of evolution, the strategy of catching prey would have been an important part of survival in a constantly changing environment. A prediction mechanism would have developed to compensate for any delay in the sensory-motor system. In a previous study, “proactive control” was found, in which the motion of the hands preceded the virtual moving target. These results implied that the positive phase shift of the hand motion represents the proactive nature of the visual-motor control system, which attempts to minimize the brief error in the hand motion when the target changes position unexpectedly. In our study, a visual target moves in circle (13 cm diameter) on a computer screen, and each subject is asked to keep track of the target’s motion by the motion of a cursor. As the frequency of the target increases, a rhythmic component was found in the velocity of the cursor in spite of the fact that the velocity of the target was constant. The generation of a rhythmic component cannot be explained simply as a feedback mechanism for the phase shifts of the target and cursor in a sensory-motor system. Therefore, it implies that the rhythmic component was generated to predict the velocity of the target, which is a feed-forward mechanism in the sensory-motor system. Here, we discuss the generation of the rhythmic component and its roll in the feed-forward mechanism.

The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

Mutual dependency grid for stakeholder mapping: a component-based approach to supply chain participant analysis

Stakeholder analysis plays a critical role in business analysis. However, the majority of the stakeholder identification and analysis methods focus on the activities and processes and ignore the artefacts being processed by human beings. By focusing on the outputs of the organisation, an artefact-centric view helps create a network of artefacts, and a component-based structure of the organisation and its supply chain participants. Since the relationship is based on the components, i.e. after the stakeholders are identified, the interdependency between stakeholders and the focal organisation can be measured. Each stakeholder is associated with two types of dependency, namely the stakeholder’s dependency on the focal organisation and the focal organisation’s dependency on the stakeholder. We identify three factors for each type of dependency and propose the equations that calculate the dependency indexes. Once both types of the dependency indexes are calculated, each stakeholder can be placed and categorised into one of the four groups, namely critical stakeholder, mutual benefits stakeholder, replaceable stakeholder, and easy care stakeholder. The mutual dependency grid and the dependency gap analysis, which further investigates the priority of each stakeholder by calculating the weighted dependency gap between the focal organisation and the stakeholder, subsequently help the focal organisation to better understand its stakeholders and manage its stakeholder relationships.

Analysis of diffusion tensor magnetic resonance imaging data using principal component analysis

An analysis method for diffusion tensor (DT) magnetic resonance imaging data is described, which, contrary to the standard method (multivariate fitting), does not require a specific functional model for diffusion-weighted (DW) signals. The method uses principal component analysis (PCA) under the assumption of a single fibre per pixel. PCA and the standard method were compared using simulations and human brain data. The two methods were equivalent in determining fibre orientation. PCA-derived fractional anisotropy and DT relative anisotropy had similar signal-to-noise ratio (SNR) and dependence on fibre shape. PCA-derived mean diffusivity had similar SNR to the respective DT scalar, and it depended on fibre anisotropy. Appropriate scaling of the PCA measures resulted in very good agreement between PCA and DT maps. In conclusion, the assumption of a specific functional model for DW signals is not necessary for characterization of anisotropic diffusion in a single fibre.

Component-resolved bleaching spectra of quartz optically stimulated luminescence: preliminary results and implications for dating

Bleaching spectra of the ‘fast’ and ‘medium’ optically stimulated luminescence (OSL) components of quartz are reported. A dependence of photoionization cross-section, σ, on wavelength was observed for the fast and medium components and a significant difference in their responses to stimulation wavelength was found. The ratio of the fast and medium photoionization cross-sections, σfast/σmedium, varied from 30.6 when stimulated with View the MathML source light to 1.4 at View the MathML source. At View the MathML source the fast and medium photoionization cross-sections were found to be sufficiently different that infrared bleaching at raised temperatures allowed the selective removal of the fast component with negligible depletion of the medium. A method for optically separating the OSL components of quartz is suggested, based on the wavelength dependence of photoionization cross-sections.

Potential of the slow component of quartz OSL for age determination of sedimentary samples

The slow component of quartz OSL exhibits a high thermal stability, and, in many of the samples studied, a high dose saturation level (several hundreds or, even thousands, of Grays). These properties suggest that the slow component has potential as a long-range dating tool. Initial attempts have been made to obtain equivalent doses for a number of sedimentary samples. Single- and multiple-aliquot techniques were modified for use with the slow component. The results indicate that there is a good potential for sediment dating, particularly for samples of significant age. Experiments concerning the optical resetting of the slow component suggest that, given its slow optical depletion rate, dating may be restricted to aeolian sediments.

Variability of marine aerosol fine-mode fraction and estimates of anthropogenic aerosol component over cloud-free oceans from the Moderate Resolution Imaging Spectroradiometer (MODIS)

In this study, we examine seasonal and geographical variability of marine aerosol fine-mode fraction ( fm) and its impacts on deriving the anthropogenic component of aerosol optical depth (ta) and direct radiative forcing from multispectral satellite measurements. A proxy of fm, empirically derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 5 data, shows large seasonal and geographical variations that are consistent with the Goddard Chemistry Aerosol Radiation Transport (GOCART) and Global Modeling Initiative (GMI) model simulations. The so-derived seasonally and spatially varying fm is then implemented into a method of estimating ta and direct radiative forcing from the MODIS measurements. It is found that the use of a constant value for fm as in previous studies would have overestimated ta by about 20% over global ocean, with the overestimation up to �45% in some regions and seasons. The 7-year (2001–2007) global ocean average ta is 0.035, with yearly average ranging from 0.031 to 0.039. Future improvement in measurements is needed to better separate anthropogenic aerosol from natural ones and to narrow down the wide range of aerosol direct radiative forcing.

The stochastic component in choice and regression to the mean

In this article, we illustrate experimentally an important consequence of the stochastic component in choice behaviour which has not been acknowledged so far. Namely, its potential to produce ‘regression to the mean’ (RTM) effects. We employ a novel approach to individual choice under risk, based on repeated multiple-lottery choices (i.e. choices among many lotteries), to show how the high degree of stochastic variability present in individual decisions can distort crucially certain results through RTM effects. We demonstrate the point in the context of a social comparison experiment.

Global runoff routing with the hydrological component of the ECMWF NWP system

A global river routing scheme coupled to the ECMWF land surface model is implemented and tested within the framework of the Global Soil Wetness Project II, to evaluate the feasibility of modelling global river runoff at a daily time scale. The exercise is designed to provide benchmark river runoff predictions needed to verify the land surface model. Ten years of daily runoff produced by the HTESSEL land surface scheme is input into the TRIP2 river routing scheme in order to generate daily river runoff. These are then compared to river runoff observations from the Global Runoff Data Centre (GRDC) in order to evaluate the potential and the limitations. A notable source of inaccuracy is bias between observed and modelled discharges which is not primarily due to the modelling system but instead of to the forcing and quality of observations and seems uncorrelated to the river catchment size. A global sensitivity analysis and Generalised Likelihood Uncertainty Estimation (GLUE) uncertainty analysis are applied to the global routing model. The ground water delay parameter is identified as being the most sensitive calibration parameter. Significant uncertainties are found in results, and those due to parameterisation of the routing model are quantified. The difficulty involved in parameterising global river discharge models is discussed. Detailed river runoff simulations are shown for the river Danube, which match well observed river runoff in upstream river transects. Results show that although there are errors in runoff predictions, model results are encouraging and certainly indicative of useful runoff predictions, particularly for the purpose of verifying the land surface scheme hydrologicly. Potential of this modelling system on future applications such as river runoff forecasting and climate impact studies is highlighted. Copyright © 2009 Royal Meteorological Society.

The projected hand illusion: component structure in a community sample, and association with demographics, cognition and psychotic-like experiences

The projected hand illusion (PHI) is a variant of the rubber hand illusion (RHI), and both are commonly used to study mechanisms of self-perception. A questionnaire was developed by Longo et al. (2008) to measure qualitative changes in the RHI. Such psychometric analyses have not yet been conducted on the questionnaire for the PHI. The present study is an attempt to validate minor modifications of the questionnaire of Longo et al. to assess the PHI in a community sample (n = 48) and to determine the association with selected demographic (age, sex, years of education), cognitive (Digit Span), and clinical (psychotic-like experiences) variables. Principal components analysis on the questionnaire data extracted four components: Embodiment of “Other” Hand, Disembodiment of Own Hand, Deafference, and Agency—in both synchronous and asynchronous PHI conditions. Questions assessing “Embodiment” and “Agency” loaded onto orthogonal components. Greater illusion ratings were positively associated with being female, being younger, and having higher scores on psychotic-like experiences. There was no association with cognitive performance. Overall, this study confirmed that self-perception as measured with PHI is a multicomponent construct, similar in many respects to the RHI. The main difference lies in the separation of Embodiment and Agency into separate constructs, and this likely reflects the fact that the “live” image of the PHI presents a more realistic picture of the hand and of the stroking movements of the experimenter compared with the RHI.

The importance of wind and buoyancy forcing for the boundary density variations and the geostrophic component of the AMOC at 26°N

It is widely thought that changes in both the surface buoyancy fluxes and wind stress drive variability in the Atlantic meridional overturning circulation (AMOC), but that they drive variability on different time scales. For example, wind forcing dominates short-term variability through its effects on Ekman currents and coastal upwelling, whereas buoyancy forcing is important for longer time scales (multiannual and decadal). However, the role of the wind forcing on multiannual to decadal time scales is less clear. Here the authors present an analysis of simulations with the Nucleus for European Modelling of the Ocean (NEMO) ocean model with the aim of explaining the important drivers of the zonal density gradient at 26°N, which is directly related to the AMOC. In the experiments, only one of either the wind stress or the buoyancy forcing is allowed to vary in time, whereas the other remains at its seasonally varying climatology. On subannual time scales, variations in the density gradient, and in the AMOC minus Ekman, are driven largely by local wind-forced coastal upwelling at both the western and eastern boundaries. On decadal time scales, buoyancy forcing related to the North Atlantic Oscillation dominates variability in the AMOC. Interestingly, however, it is found that wind forcing also plays a role at longer time scales, primarily impacting the interannual variability through the excitation of Rossby waves in the central Atlantic, which propagate westward to interact with the western boundary, but also by modulating the decadal time-scale response to buoyancy forcing.