Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs:implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs

FRET (fluorescence resonance energy transfer) and co-immunoprecipitation studies confirmed the capacity of beta-arrestin 2 to self-associate. Amino acids potentially involved in direct protein-protein interaction were identified via combinations of spot-immobilized peptide arrays and mapping of surface exposure. Among potential key amino acids, Lys(285), Arg(286) and Lys(295) are part of a continuous surface epitope located in the polar core between the N- and C-terminal domains. Introduction of K285A/R286A mutations into beta-arrestin 2-eCFP (where eCFP is enhanced cyan fluorescent protein) and beta-arrestin 2-eYFP (where eYFP is enhanced yellow fluorescent protein) constructs substantially reduced FRET, whereas introduction of a K295A mutation had a more limited effect. Neither of these mutants was able to promote beta2-adrenoceptor-mediated phosphorylation of the ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs (mitogen-activated protein kinases). Both beta-arrestin 2 mutants displayed limited capacity to co-immunoprecipitate ERK1/2 and further spot-immobilized peptide arrays indicated each of Lys(285), Arg(286) and particularly Lys(295) to be important for this interaction. Direct interactions between beta-arrestin 2 and the beta2-adrenoceptor were also compromised by both K285A/R286A and K295A mutations of beta-arrestin 2. These were not non-specific effects linked to improper folding of beta-arrestin 2 as limited proteolysis was unable to distinguish the K285A/R286A or K295A mutants from wild-type beta-arrestin 2, and the interaction of beta-arrestin 2 with JNK3 (c-Jun N-terminal kinase 3) was unaffected by the K285A/R286A or L295A mutations. These results suggest that amino acids important for self-association of beta-arrestin 2 also play an important role in the interaction with both the beta2-adrenoceptor and the ERK1/2 MAPKs. Regulation of beta-arrestin 2 self-association may therefore control beta-arrestin 2-mediated beta2-adrenoceptor-ERK1/2 MAPK signalling.

The organisation of innovation: collaboration, cooperation and multifunctional groups in UK and German manufacturing

Marked differences exist between the institutional and social context for innovation in the UK and Germany. The question addressed here is how these different contexts affect the objectives and organisation of innovation in UK and German manufacturing. In particular, the paper examines the extent to which UK and German plants engage in inter-plant collaboration and cooperation and multifunctional working as part of their innovative activity, and explores the reasons for differences in these patterns of involvement. The investigation is based on a large-scale, comparative survey of manufacturing plants in the two countries. In Germany, institutional and social norms are found to encourage collaborative inter-plant innovation, but aspects of the German skills training and industrial relations systems make the adoption of more flexible internal systems more difficult. In the UK, by contrast, the more adversarial nature of inter-firm relations makes it more difficult to establish external collaborations based on mutual trust, but less restrictive labour market structures make it easier for UK plants to adopt multifunctional working. This is linked to differences in attitudes to the property rights and transaction cost problems inherent in innovation.

The role of self-regulation as a meta-competency in developing leaders: a longitudinal field experimental study

The question of how to develop leaders so that they are more effective in a variety of situations, roles and levels has inspired a voluminous amount of research. While leader development programs such as executive coaching and 360-degree feedback have been widely practiced to meet this demand within organisations, the research in this area has only scratched the surface. Drawing from the past literature and leadership practices, the current research conceptualised self-regulation, as a metacompetency that would assist leaders to further develop the specific competencies needed to perform effectively in their leadership role, leading to an increased rating of leader effectiveness and to enhanced group performance. To test this conceptualisation, a longitudinal field experimental study was conducted across ten months with a pre- and two post-test intervention designs with a matched control group. This longitudinal field experimental compared the difference in leader and team performance after receiving self-regulation intervention that was delivered by an executive coach. Leaders in experimental group also received feedback reports from 360-degree feedback at each stage. Participants were 40 leaders, 155 followers and 8 supervisors. Leaders’ performance was measured using a multi-source perceptual measure of leader performance and objective measures of team financial and assessment performance. Analyses using repeated measure of ANCOVA on pre-test and two post-tests responses showed a significant difference between leader and team performance between experimental and control group. Furthermore, leader competencies mediated the relationship between self-regulation and performance. The implications of these findings for the theory and practice of leadership development training programs and the impact on organisational performance are discussed.

Reading skills are related to global, but not local, acoustic pattern perception

Although reading ability has been related to the processing of simple pitch features such as isolated transitions or continuous modulation spoken language also contains complex patterns of pitch changes that are important for establishing stress location and for segmenting the speech stream. These aspects of spoken language processing depend critically on pitch pattern (global structure) rather than on absolute pitch values (local structure). Here we show that the detection of global structure, and not local structure, is predictive of performance on measures of phonological skill and reading ability, which supports a critical importance of pitch contour processing in the acquisition of literacy.

Anger rumination and self-reported aggression amongst British and Hong Kong Chinese athletes: a cross cultural comparison

Previous work has determined relationships between provocation, anger rumination, and aggression in British athletes (Maxwell, 2004); however, the reliability of these findings and their generality across diverse cultures has not been examined. Therefore, a comparison of British and Hong Kong (HK) Chinese athletes’ propensity for rumination and aggression was undertaken. Provocation and thoughts of revenge were significantly associated with the self-reported aggression of both British and HK Chinese athletes. Frequency of aggression was similar across cultures except for a tendency for British male contact sport athletes to report greater frequency of aggressive behaviour. HK Chinese athletes tended to report higher frequencies of thoughts relating to understanding the causes of anger and higher incidence of perceived provocation. It was concluded that the pattern of aggressive behaviour was similar across the two cultures when opportunities for aggression are infrequent, but that HK Chinese athletes may inhibit aggressive responding even when opportunities are frequent.

Technological and organisational change in small- to medium-sized manufacturing companies:a learning organisation perspective

This paper examines the extent to which a learning organisation perspective is attainable in small- to medium-sized manufacturing companies. An audit tool is developed from the literature on organisational learning and recognised processes that lead towards becoming a learning organisation. The paper focuses on the application of the audit tool in three UK automotive component suppliers which are all experiencing pressures for change imposed by the major vehicle manufacturers. The main changes are concerned with tiering of the supply chain and substantial delegation of responsibilities to component suppliers including an increasing emphasis on innovation and continuous improvement. The companies presented in the paper are taken from a research project into the impact of changes in supply chain relationships on the operation of small- and medium-sized manufacturing firms in the West Midlands region of the UK. The ways in which the companies are responding to change are presented together with the results of a self-assessment using the developed audit tool. These results suggest that companies of this type tend to focus on change in those areas that involve least challenge to the established power and authority of management.

Individual differences in cognitive style and their effects on task and social orientations of self-managed work teams

When assembling self-managing work teams, the personalities of team members are often overlooked. One personality variable known to be critical for effective decision making in teams is cognitive style. This study sought to examine how differences and similarities in analytic/intuitive cognitive styles affected the behavior of team members on the task/emotionally expressive dimension identified by Bales. As hypothesized, intuitive individuals and homogeneous intuitive teams were found to initiate more social-emotional acts. Contrary to expectations, intuitive rather than analytic individuals and homogeneous intuitive rather than analytic teams engaged in more task-oriented behaviors. Teams also tended to select intuitive individuals as leaders. The possibility that different combinations of styles may be important for overall team effectiveness was subsequently discussed, and it was suggested that this may depend on whether the nature of the work environment is relatively well structured and mechanistic or relatively unstructured and organic.

The effect of PEO length on the self-assembly of poly(ethylene oxide)−tetrapeptide conjugates prepared by “click” chemistry

Two series of poly(ethylene oxide)-tetrapeptide conjugates have been prepared using a “Click” reaction between an alkyne-modified tetra(phenylalanine) or tetra(valine) and various azide-terminated poly(ethylene oxide) (PEO) oligomers. Three different PEO precursors were used to prepare these conjugates, with number-average molecular weights of 350, 1200, and 1800 Da. Assembly of mPEO-F4-OEt and mPEO-V4-OEt conjugates was achieved by dialysis of a THF solution of the conjugate against water or by direct aqueous rehydration of a thin film. The PEO length has a profound effect on the outcome of the self-assembly, with the F4 conjugates giving rise to nanotubes, fibers, and wormlike micelles, respectively, as the length of the PEO block is increased. For the V4 series, the propensity to form ß-sheets dominates, and hence, the self-assembled structures are reminiscent of those formed by peptides alone, even at the longer PEO lengths. Thus, this systematic study demonstrates that the self-assembly of PEO-peptides depends on both the nature of the peptides and the relative PEO block length.

Pattern visual evoked potentials in man and tetrahydrobiopterin metabolism

The P2 visual evoked response in man has a cholinergic component while the P100 response has not. The P100 latency is significantly decreased after an oral dose of phenylalanine in man while the P2 signal is unaffected. Analyses of the P100 decrease shows no correlation with tyrosine levels but a significant positive correlation with plasma ane urine levels. A small group shows a P100 delay which correlated with increased neopterin levels only. Increased plasma total biopterins in man following a phenylalanine dose are due to rapidly increased tetrahydrobiopterin synthesis in the liver.

Biochemical markers and contact lens wear

The project objective was to develop a reliable selection procedure to match contact lens materials with individual wearers by the identification of a biochemical marker for assessment of in-eye performance of contact lenses. There is a need for such a procedure as one of the main reasons for contact lens wearers ceasing wearing contact lenses is poor end of day comfort i.e. the lenses become intolerable to the wearer as the day progresses. The selection of an optimal material for individual wearers has the potential benefit to reduce drop Qut, hence increasing the overall contact lens population, and to improve contact lens comfort for established wearers. Using novel analytical methods and statistical techniques, we were able to investigate the interactions between the composition of the tear film and of the biofilm deposited on the contact lenses and contact lens performance. The investigations were limited to studying the lipid components of the tear film; the lipid layer, which plays a key role in preventing evaporation and stabilising the tear film, has been reported to be significantly thinner and of different mixing characteristics during contact lens wear. Different lipid families were found to influence symptomatology, in vivo tear film structure and stability as well as ocular integrity. Whereas the symptomatology was affected by both the tear film lipid composition and the nature of the lipid deposition, the structure of the tear film and its stability were mainly influenced by the tear film lipid composition. The ocular integrity also appeared to be influenced by the nature of the lipid deposition. Potential markers within the lipid species have been identified and could be applied as follows: When required in order to identify a problematic wearer or to match the contact lens material to the contact lens wearer, tear samples collected by the clinician could be dispatched to an analytical laboratory where lipid analysis could be carried out by HPLC. A colorimetric kit based on the lipid markers could also be developed and used by clinician directly in the practice; such a kit would involve tear sampling and classification according to the colour into "Problem", "Border line" and "Good" contact lens wearers groups. A test kit would also have wider scope for marketing in other areas such as general dry-eye pathology.

Self-attentional processes in anxiety:an experimental study

Self-attention research has demonstrated a relationship between dispositional self-focus, anxiety proneness and fear arousal. In addition, the effect of self-focus manipulations on approach-avoidance tasks involving a feared stimulus are strikingly similar to the effects obtained from manipulation of other cognitive factors such as perceived self-efficacy. A number of experiments were designed to explore the relationship between self-focused attention and ffilxiety. Data from the experiments demonstrate that self-attention influences a variety of cognitive variables which have been considered as central factors in anxiety. Concomitants of self-focus are increased awareness of physiological arousal and overestimation of such arousal, the identification of self-discrepancies, cognitive failures and performance deficits and the activation of physical threat concepts in memory. These factors are conceptualised as central in the negative evaluation of physiological arousal and coping resources in anxiety. Clinically anxious individuals typically have high scores in dispositional self-consciousness and body-consciousness. In patients suffering from generalised anxiety or panic disorders maladaptive self-focusing tendencies can be related to specific life stressors which render aspects of the self salient. An analysis of the ideational component of anxiety revealed three subcomponents; negative social ideation (worry about other people's reaction to the self), negative somatic ideation (worry about physical symptoms and health) and obsessional ideation (the experience of uncontrollable and repetitive thoughts) which were differentially associated with measures of dispositional self-focus. The frequency and content of an.xious w-orry is associated with specific self-focusing tendencies. It is proposed that the 'attentional style' of the individual is an important determinant of the nature and intensity of their affective response in a threatening situation. A self-attentional model of anxiety is proposed and the complex interaction between self-focus and other cognitive factors in anxiety such as appraisal of arousal and coping resources and perceived levels of self-efficacy is discussed. The model presents new directions for research and therapeutic intervention in anxiety.

Experiments and analysis of combined diffraction and self diffraction effects in a nematic liquid crystal cell

The potential for nonlinear optical processes in nematic-liquid-crystal cells is great due to the large phase changes resulting from reorientation of the nematic-liquid-crystal director. Here the combination of diffraction and self-diffraction effects are studied simultaneously by the use of a pair of focused laser beams which are coincident on a homeotropically aligned liquid-crystal cell. The result is a complicated diffraction pattern in the far field. This is analyzed in terms of the continuum theory for liquid crystals, using a one-elastic-constant approximation to solve the reorientation profile. Very good comparison between theory and experiment is obtained. An interesting transient grating, existing due to the viscosity of the liquid-crystal material, is observed in theory and practice for large cell-tilt angles.

Observations of diffraction and self diffraction effects during two wave mixing in a nematic liquid crystal

We report observations of the diffraction pattern resulting when a nematic liquid crystal is illuminated with two equal power, high intensity beams of light from an Ar+ laser. The time evolution of the pattern is followed from the initial production of higher diffraction orders to a final striking display arising as a result of the self-diffraction of the two incident beams. The experimental results are described with good approximation by a model assuming a phase distribution at the output plane of the liquid crystal in the form of the sum of a gaussian and a sinusoid.

Establishment of a reedbed within a created surface water fed wetland nature reserve

In the early 1990's, outline designs for two wetland nature reserves were being prepared: the Teeside International Nature Reserve (TINR) and the Cardiff Bay Barrage Environmental Compensation Measures at Redwick, Gwent. The initial design for both proposals identified reedbed as a desirable habitat for establishment. The initial design works identified the importance of reedbed evapotranspiration [ET(Reed)] within the water budget, however, literature searches identified a paucity of information on this parameter. Field experiments for the measurement of ET(Reed) from Phragmites australis are described for three sites distributed across England and Wales. Reference Crop Evapotranspiration (ETo) was calculated using techniques recommended by the Food and Agriculture Organisation. A technique for the calculation of a reedbed crop coefficient [Kc(Reed)[, from ET(Reed) and ETo data is discussed. Kc(Reed) values produced in the project were found to be similar to those developed previously in continental Europe. Mean monthly and crop development stage Kc(Reed) values are presented which are applicable in the UK and possibly worldwide. A conceptual hydrological model of surface water fed reedbed systems is developed, and used to calculate the hydrological sustainability of reedbed creation areas in the UK. Finally, the water budget model is verified using data from a small clay catchment located on the TINR. In addition, a methodology is developed for the hydrological design of surface water fed reedbed systems, and recommendations required for the feasibility, design and establishment stage of reedbed creation sites. Further research needs are also identified.

Safety culture during major organisational change

This research examines the effect of major changes, in the external context, on the safety culture of a UK generating company. It was focused on an organisation which was originally part of the state owned Central Electricity Generating Board and which, by the end of the research period, was a self-contained generating company, operating in a competitive market and a wholly owned subsidiary of a US utility. The research represents an attempt to identify the nature and culture of the original organisation and to identify, analyse and explain the effects of the forces of change in moulding the final organisation. The research framework employed a qualitative methodology to investigate the effects of change, supported by a safety culture questionnaire, based on factors identified in the third report of the ACSNI Human Factors Study Group; Organising for Safety, as being indicators of safety culture. An additional research objective was to assess the usefulness of the ACSNI factors as indicators of safety culture. Findings were that the original organisation was an engineering dominated technocracy with a technocentric safety culture. Values and beliefs were very strongly held and resistant to change and much of the original safety culture survived unchanged into the new organisation. The effects of very long periods of uncertainty about the future were damaging to management/worker relationships but several factors were identified which effectively insulated the organisation from any of the effects of change. The forces of change had introduced a beneficial appreciation of the crucial relationship between safety risk assessment and commercial risk assessment.Although the technical strength of the original safety culture survived, so did the essential weakness of a low level of appreciation of the human behavioural aspects of safety. This led to a limited, functionalist world view of safety culture, which assumed that cultural change was simpler to achieve than was the case and an inability to make progress in certain areas which were essentially behavioural problems.The factors identified by ACSNI provided a useful basis for the site research methodology and for identifying areas of relative strength and weakness in the site safety arrangements.