The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility

The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition. © 2014 Macmillan Publishers Limited. All rights reserved.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

Capabilities for strategic flexibility:a cognitive content framework

Different forms of strategic flexibility allow for reactive adaptation to different changing environments and the proactive driving of change. It is therefore becoming increasingly important for decision makers to not only possess marketing capabilities, but also the capabilities for strategic flexibility in its various forms. However, our knowledge of the relationships between decision makers’ different ways of thinking and their capabilities for strategic flexibility is limited. This limitation is constraining research and understanding. In this article we develop a theoretical cognitive content framework that postulates relationships between different ways of thinking about strategy and different information-processing demands. We then outline how the contrasting beliefs of decision makers may influence their capabilities to generate different hybrid forms of strategic flexibility at the cognitive level. Theoretically, the framework is embedded in resource-based theory, personal construct theory and schema theory. The implications for research and theory are discussed.

A qualitative investigation into leader behavioural flexibility

Purpose – The current research aims to determine to what extent Australian managers are behaviourally flexible and to identify what factors are associated with the development of leader behavioural flexibility (LBF) and its contribution to positive organisational outcomes. Design/methodology/approach – Because of the exploratory nature of the questions to be addressed, a qualitative approach to data collection was selected. In particular, the grounded theory methodology was utilised due to its ability to aid with the theory building process. Semi-structured interviews based on the critical incident interview technique were used as the data source. Findings – The findings illustrate that the Australian managers who participated in this study exhibited significant degrees of LBF. The results also suggest that education level and group size may be antecedents to LBF. In addition, it appears that leader-member exchange may mediate the relationship between LBF and positive organisational outcomes, while social intelligence may moderate this relationship. Research limitations/implications – The current research makes several contributions in terms of theoretical development and reveals a richer insight into the underlying processes associated with the relationship between LBF and positive organisational outcomes. Practical implications – As the current research was conducted in the field with 20 practising organisational managers, the findings also highlight some important practical applications regarding LBF. Originality/value – Although previous studies have been able to establish a relationship between LBF and positive organisational outcomes, they have explained very little about the processes associated with this relationship. The present study attempted to uncover some of these processes.

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

Ossification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice.

Organisational slack resources, the definitions and consequences for business flexibility and performance : an empirical investigation

Slack resources are recognised to be those spare capabilities and assets of the organisation that are variable reclaimable for re-deployment. They represent under utilised and hidden spare energies within a company that may be recaptured and employed for a variety of tasks. However their positive contribution to organisational success has been a contentious claim that has provoked the intuitive argument that slack resources are inefficiency and are to be eradicated. The counter argument has been that very efficient organisations are inflexible and therefore incapable of being responsive to an increasingly dynamic environment. Therefore this work compares and contrasts three distinctive industries in a holistic manner and maps the impact of environmental flux on the firm, its subsequent disruptive ripples through the organisation and its absorption by slack resources. Through this process it is demonstrated that slack resources do positively contribute to organisational performance and subsequently the ability of slack to promote sustained competitive advantage is also identified. The major findings of this work are listed. 1. This work has developed and perfected a new research model that aids the investigation of the internal behaviours and consequences of Slack Resources. 2. Supported by argument a new variable of Soft Slack was developed. Its validity was demonstrated in its ability to capture the contribution of intangible assets, such as education, experience, spare management time and further training, to the extant levels of Organisational Hard Slack resources. 3. The validity of Soft Slack was further supported when its contribution to organisational Flexibility was also established. 4. The original argument that Slack Resources enhance organisational Performance has been further developed. It is now evidenced that Slack Resources facilitate Organisational Flexibility and by this process enhances Organisational Performance.

Public sector investment appraisal:the place of flexibility in the decision making process

This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

"Marketing and flexibility":debates past present and future

Special issue editorial: Purpose – The purpose of this paper is to outline the articles presented in the Special Issue on the topic of “Marketing and flexibility”, and to discuss key issues associated with major debates relating to flexibility in order to position the articles within a wider context and highlight some key issues for further research. Design/methodology/approach – Themes in prior research relating to “Marketing and flexibility” are documented and the growth of research interest into strategic flexibility is tabulated. The contributions of each article are briefly discussed. Findings – There has been a steady growth of research interest into flexibility. To provide an example of this growth, the increase in the number of articles published on the topic of strategic flexibility in scholarly journals is highlighted over a 20-year period. Key issues in prior research such as alternative definitions and the different postulated relationships between market orientation and strategic flexibility are revealed, as are issues for future research. Originality/value – Key issues relating to research into flexibility for marketing scholars are revealed.

Antecedents of strategic flexibility:management cognition, firm resources and strategic options

Purpose: Current conceptualisations of strategic flexibility and its antecedents are theory-driven, which has resulted in a lack of consensus. To summarise this domain the paper aims to develop and present an a priori conceptual model of the antecedents and outcomes of strategic flexibility. Discussion and insights into the conceptual model, and the relationships specified, are made through a novel qualitative empirical approach. The implications for further research and a framework for further theoretical development are presented. Design/methodology/approach: An exploratory qualitative research design is used applying multiple data collection techniques in a branch network of a large regional retailer in the UK. The development of strategic options and the complex relationship to strategic flexibility is investigated. Findings: The number and type of strategic options developed by managers impact on the degree of strategic flexibility and also on the ability of the firm to achieve competitive differentiation. Additionally, the type of strategic option implemented by managers is dependent on the competitive situation faced at a local level. Evidence of managers' limited perception of competition was identified based on their spatial embeddedness. Research limitations/implications: A single, in-depth case study was used. The data gathered is rich and appropriate for the exploratory approach adopted here. However, generalisability of the findings is limited. Practical implications: Strategic flexibility is rooted in the ability of front-line mangers to develop and implement strategic options; this in turn facilitates competitive differentiation. Originality/value: The research presented is unique in this domain on two accounts. First, theory is developed by presenting an a priori conceptual model, and testing through in-depth qualitative data gathering. Second, insights into strategic flexibility are presented through an examination of managerial cognition, resources and strategic option generation using cognitive mapping and laddering technique. © Emerald Group Publishing Limited.