Delineation and modelling of a nucleolar retention signal in the coronavirus nucleocapsid protein

Unlike nuclear localization signals, there is no obvious consensus sequence for the targeting of proteins to the nucleolus. The nucleolus is a dynamic subnuclear structure which is crucial to the normal operation of the eukaryotic cell. Studying nucleolar trafficking signals is problematic as many nucleolar retention signals (NoRSs) are part of classical nuclear localization signals (NLSs). In addition, there is no known consensus signal with which to inform a study. The avian infectious bronchitis virus (IBV), coronavirus nucleocapsid (N) protein, localizes to the cytoplasm and the nucleolus. Mutagenesis was used to delineate a novel eight amino acid motif that was necessary and sufficient for nucleolar retention of N protein and colocalize with nucleolin and fibrillarin. Additionally, a classical nuclear export signal (NES) functioned to direct N protein to the cytoplasm. Comparison of the coronavirus NoRSs with known cellular and other viral NoRSs revealed that these motifs have conserved arginine residues. Molecular modelling, using the solution structure of severe acute respiratory (SARS) coronavirus N-protein, revealed that this motif is available for interaction with cellular factors which may mediate nucleolar localization. We hypothesise that the N-protein uses these signals to traffic to and from the nucleolus and the cytoplasm.

A field study of factors influencing the concentrations of a traffic-related pollutant in the vicinity of a complex urban junction

The paper describes a field study focused on the dispersion of a traffic-related pollutant within an area close to a busy intersection between two street canyons in Central London. Simultaneous measurements of airflow, traffic flow and carbon monoxide concentrations ([CO]) are used to explore the causes of spatial variability in [CO] over a full range of background wind directions. Depending on the roof-top wind direction, evidence of both flow channelling and recirculation regimes were identified from data collected within the main canyon and the intersection. However, at the intersection, the merging of channelled flows from the canyons increased the flow complexity and turbulence intensity. These features, coupled with the close proximity of nearby queuing traffic in several directions, led to the highest overall time-average measured [CO] occurring at the intersection. Within the main street canyon, the data supported the presence of a helical flow regime for oblique roof-top flows, leading to increased [CO] on the canyon leeward side. Predominant wind directions led to some locations having significantly higher diurnal average [CO] due to being mostly on the canyon leeward side during the study period. For all locations, small changes in the background wind direction could cause large changes in the in-street mean wind angle and local turbulence intensity, implying that dispersion mechanisms would be highly sensitive to small changes in above roof flows. During peak traffic flow periods, concentrations within parallel side streets were approximately four times lower than within the main canyon and intersection which has implications for controlling personal exposure. Overall, the results illustrate that pollutant concentrations can be highly spatially variable over even short distances within complex urban geometries, and that synoptic wind patterns, traffic queue location and building topologies all play a role in determining where pollutant hot spots occur.

Moist singular vectors and the predictability of some high impact European cyclones

The ECMWF full-physics and dry singular vector (SV) packages, using a dry energy norm and a 1-day optimization time, are applied to four high impact European cyclones of recent years that were almost universally badly forecast in the short range. It is shown that these full-physics SVs are much more relevant to severe cyclonic development than those based on dry dynamics plus boundary layer alone. The crucial extra ingredient is the representation of large-scale latent heat release. The severe winter storms all have a long, nearly straight region of high baroclinicity stretching across the Atlantic towards Europe, with a tongue of very high moisture content on its equatorward flank. In each case some of the final-time top SV structures pick out the region of the actual storm. The initial structures were generally located in the mid- to low troposphere. Forecasts based on initial conditions perturbed by moist SVs with opposite signs and various amplitudes show the range of possible 1-day outcomes for reasonable magnitudes of forecast error. In each case one of the perturbation structures gave a forecast very much closer to the actual storm than the control forecast. Deductions are made about the predictability of high-impact extratropical cyclone events. Implications are drawn for the short-range forecast problem and suggestions made for one practicable way to approach short-range ensemble forecasting. Copyright © 2005 Royal Meteorological Society.

Intensities in the v7, v8 and v9 bands of CH2NH, and the harmonic force field of methyleneimine

A high resolution Fourier transform infrared spectrum of methyleneimine, HN=CH2, has been obtained in the gas phase in the region 700 to 1300 cm−1. The rovibrational line intensities of the three lowest fundamentals ν7 (A′), ν8 (A″), and ν9 (A″) have been simulated including all Coriolis interactions between the three bands, and by fitting the observed spectrum the relative signs and magnitudes of the vibrational transition moments have been determined. All of the available spectroscopic data have been used to determine the harmonic force field of methyleneimine.

Radiative forcing due to changes in ozone and methane caused by the transport sector

The year 2000 radiative forcing (RF) due to changes in O3 and CH4 (and the CH4-induced stratospheric water vapour) as a result of emissions of short-lived gases (oxides of nitrogen (NOx), carbon monoxide and non-methane hydrocarbons) from three transport sectors (ROAD, maritime SHIPping and AIRcraft) are calculated using results from five global atmospheric chemistry models. Using results from these models plus other published data, we quantify the uncertainties. The RF due to short-term O3 changes (i.e. as an immediate response to the emissions without allowing for the long-term CH4 changes) is positive and highest for ROAD transport (31mWm-2) compared to SHIP (24 mWm-2) and AIR (17 mWm-2) sectors in four of the models. All five models calculate negative RF from the CH4 perturbations, with a larger impact from the SHIP sector than for ROAD and AIR. The net RF of O3 and CH4 combined (i.e. including the impact of CH4 on ozone and stratospheric water vapour) is positive for ROAD (+16(±13)(one standard deviation) mWm-2) and AIR (+6(±5) mWm-2) traffic sectors and is negative for SHIP (-18(±10) mWm-2) sector in all five models. Global Warming Potentials (GWP) and Global Temperature change Potentials (GTP) are presented for AIR NOx emissions; there is a wide spread in the results from the 5 chemistry models, and it is shown that differences in the methane response relative to the O3 response drive much of the spread.

Individual variation in psychological and psychomotor symptoms following smoking cessation: the implications for treatment

Some commonly experienced signs and symptoms occur during abstinence from tobacco, but specific signs and symptoms and their intensity vary greatly from individual to individual. The aim of this study was to re-examine psychological and psychomotor symptoms in smokers in the general population, and to explore the individual variation in these. Quitting smokers (n = 123) reported their experiences pre- and post-cessation, on a questionnaire developed for the study. Analysis of variance and frequency analysis showed significant decreases between pre- and post-cessation on positive experiences (F = 9.81, p < 0.0001) but no significant change on negative experiences, suggesting a loss of pleasure rather than increased negative affect upon quitting. The variance of the pre- to post-cessation difference score suggested wide variation in the reporting of withdrawal symptoms. These results lead us to consider the implications for treatment, using cognitive therapies and moderating the significant emphasis that is at present put on withdrawal.

Attribution and the effects of expectancy: how beliefs can influence the experiences of smoking cessation

Research on smoking cessation has found consistencies and similarities during abstinence, but also that the specific signs and symptoms and their intensity vary greatly from individual to individual. One possible source of this variation is the cognitions associated with quitting. We investigated the experiences and associated cognitions in normal cessation by asking quitting smokers to rate their experiences on a questionnaire and to indicate the most likely reason for each experience. Statistical analyses confirmed that attributions to abstinence were significantly higher for increased negative experiences, and there were significantly more reattributions than would be found by chance for items associated with smoking abstinence. Significantly more attributions to abstinence were made by clinic attendees and significantly more attributions of negative experiences to abstinence were made by unaided quitters using self-help materials. These results can be interpreted in the context of attribution theory; quitters may use the cognitions available to them to attribute their negative experiences to quitting. Consequently, counsellors could use cognitive therapy to alter their clients' expectations and explanations of their experiences, and emphasise the positive outcomes of cessation. (C) 2002 Elsevier Science Ltd. All rights reserved.

Controls of carbon dioxide concentrations and fluxes above central London

Eddy-covariance measurements of carbon dioxide fluxes were taken semi-continuously between October 2006 and May 2008 at 190 m height in central London (UK) to quantify emissions and study their controls. Inner London, with a population of 8.2 million (~5000 inhabitants per km2) is heavily built up with 8% vegetation cover within the central boroughs. CO2 emissions were found to be mainly controlled by fossil fuel combustion (e.g. traffic, commercial and domestic heating). The measurement period allowed investigation of both diurnal patterns and seasonal trends. Diurnal averages of CO2 fluxes were found to be highly correlated to traffic. However changes in heating-related natural gas consumption and, to a lesser extent, photosynthetic activity that controlled the seasonal variability. Despite measurements being taken at ca. 22 times the mean building height, coupling with street level was adequate, especially during daytime. Night-time saw a higher occurrence of stable or neutral stratification, especially in autumn and winter, which resulted in data loss in post-processing. No significant difference was found between the annual estimate of net exchange of CO2 for the expected measurement footprint and the values derived from the National Atmospheric Emissions Inventory (NAEI), with daytime fluxes differing by only 3%. This agreement with NAEI data also supported the use of the simple flux footprint model which was applied to the London site; this also suggests that individual roughness elements did not significantly affect the measurements due to the large ratio of measurement height to mean building height.

Cognitive process modelling of controllers in en route air traffic control

In recent years, various efforts have been made in air traffic control (ATC) to maintain traffic safety and efficiency in the face of increasing air traffic demands. ATC is a complex process that depends to a large degree on human capabilities, and so understanding how controllers carry out their tasks is an important issue in the design and development of ATC systems. In particular, the human factor is considered to be a serious problem in ATC safety and has been identified as a causal factor in both major and minor incidents. There is, therefore, a need to analyse the mechanisms by which errors occur due to complex factors and to develop systems that can deal with these errors. From the cognitive process perspective, it is essential that system developers have an understanding of the more complex working processes that involve the cooperative work of multiple controllers. Distributed cognition is a methodological framework for analysing cognitive processes that span multiple actors mediated by technology. In this research, we attempt to analyse and model interactions that take place in en route ATC systems based on distributed cognition. We examine the functional problems in an ATC system from a human factors perspective, and conclude by identifying certain measures by which to address these problems. This research focuses on the analysis of air traffic controllers' tasks for en route ATC and modelling controllers' cognitive processes.

Nutrient sensing and signalling in plants: Potassium and phosphorus

Potassium and phosphorus are important macronutrients for crops but are often deficient in the field. Very little is known about how plants sense fluctuations in K and P and how information about K and P availability is integrated at the whole plant level into physiological and metabolic adaptations. This chapter reviews recent advances in discovering molecular responses of plants to K and P deficiency by microarray experiments. These studies provide us not only with a comprehensive picture of adaptive mechanisms, but also with a large number of transcriptional markers that can be used to identify upstream components of K and P signalling pathways. On the basis of the available information we discuss putative receptors and signals involved in the sensing and integration of K and P status both at the cellular and at the whole plant level. These involve membrane potential, voltage-dependent ion channels, intracellular Ca and pH, and transcription factors, as well as hormones and metabolites for systemic signalling. Genetic screens of reporter lines for transcriptional markers and metabolome analysis of K- and P-deficient plants are likely to further advance our knowledge in this area in the near future.

The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle.

Analysing the factors that influence tag choice based on semiotic analysis and activity theory

Social tagging has become very popular around the Internet as well as in research. The main idea behind tagging is to allow users to provide metadata to the web content from their perspective to facilitate categorization and retrieval. There are many factors that influence users' tag choice. Many studies have been conducted to reveal these factors by analysing tagging data. This paper uses two theories to identify these factors, namely the semiotics theory and activity theory. The former treats tags as signs and the latter treats tagging as an activity. The paper uses both theories to analyse tagging behaviour by explaining all aspects of a tagging system, including tags, tagging system components and the tagging activity. The theoretical analysis produced a framework that was used to identify a number of factors. These factors can be considered as categories that can be consulted to redirect user tagging choice in order to support particular tagging behaviour, such as cross-lingual tagging.