Exploring emotions and cognitions in hoarding: a Q-methodology analysis

Background: The cognitions and emotions of people prone to hoarding are key components of the dominant cognitive behavioural model of hoarding disorder. Aims: This study sought to use Q-methodology to explore the thoughts and feelings of people that are prone to hoarding, to identify whether distinct clusters of participants could be found. Method: A 49-statement Q-set was generated following thematic analysis of initial interviews (n = 2) and a review of relevant measures and literature. Forty-one participants with problematic hoarding met various study inclusion criteria and completed the Q-sort (either online or offline). A by-person factor analysis was conducted and subsequent participant clusters compared on psychometric measures of mood, anxiety, hoarding and time taken on the online task as proxy for impulsivity. Results: Four distinct participant clusters were found constituting 34/41 (82.92%) of the participants, as the Q-sorts of n = 7 participants failed to cluster. The four clusters found were ‘overwhelmed’ (n = 11 participants); ‘aware of consequences’ (n = 13 participants); ‘object complexity’ (n = 6 participants) and ‘object–affect fusion’ (n = 4 participants). The clusters did not markedly differ with regard to hoarding severity, anxiety, depression or impulsivity. Conclusions: Whilst the participant clusters reflect extant research evidence, they also reveal significant heterogeneity and so prompt the need for further research investigating emotional and cognitive differences between people prone to hoarding

Investigating and promoting trainee science teachers’ conceptual change of the nature of science with digital dialogue games “InterLoc”

The purpose of this study is to explore how an online-structured dialogue environment supported (OSDE) collaborative learning about the nature of science among a group of trainee science teachers in the UK. The software used (InterLoc) is a linear text-based tool, designed to support structured argumentation with openers and ‘dialogue moves’. A design-based research approach was used to investigate multiple sessions using InterLoc with 65 trainee science teachers. Five participants who showed differential conceptual change in terms of their Nature of Science (NOS) views were purposively selected and closely followed throughout the study by using key event recall interviews. Initially, the majority of participants held naïve views of NOS. Substantial and favourable changes in these views were evident as a result of the OSDE. An examination of the development of the five participants’ NOS views indicated that the effectiveness of the InterLoc discussions was mediated by cultural, cognitive, and experiential factors. The findings suggest that InterLoc can be effective in promoting reflection and conceptual change.InterLoc was developed by a team led by Andrew Ravenscroft with funding from the UK JISC (Joint Information Systems Committee) 'e-learning tools' programme, and from the JISC Capital Programme

Elucidating the mechanisms of cooperative calcium-calmodulin interactions: A structural systems biology approach

Background: Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. Calcium binding induces conformational transitions in calmodulin that make it specifically active to particular target proteins. The precise mechanisms underlying calcium binding to calmodulin are still, however, quite poorly understood. Results: In this study, we adopt a structural systems biology approach and develop a mathematical model to investigate various types of cooperative calcium-calmodulin interactions. We compare the predictions of our analysis with physiological dose-response curves taken from the literature, in order to provide a quantitative comparison of the effects of different mechanisms of cooperativity on calcium-calmodulin interactions. The results of our analysis reduce the gap between current understanding of intracellular calmodulin function at the structural level and physiological calcium-dependent calmodulin target activation experiments. Conclusion: Our model predicts that the specificity and selectivity of CaM target regulation is likely to be due to the following factors: variations in the target-specific Ca2+ dissociation and cooperatively effected dissociation constants, and variations in the number of Ca2+ ions required to bind CaM for target activation. © 2008 Valeyev et al; licensee BioMed Central Ltd

Classification and stability of simple homoclinic cycles in R^5

The paper presents a complete study of simple homoclinic cycles in R^5. We find all symmetry groups Gamma such that a Gamma-equivariant dynamical system in R^5 can possess a simple homoclinic cycle. We introduce a classification of simple homoclinic cycles in R^n based on the action of the system symmetry group. For systems in R^5, we list all classes of simple homoclinic cycles. For each class, we derive necessary and sufficient conditions for asymptotic stability and fragmentary asymptotic stability in terms of eigenvalues of linearisation near the steady state involved in the cycle. For any action of the groups Gamma which can give rise to a simple homoclinic cycle, we list classes to which the respective homoclinic cycles belong, thus determining conditions for asymptotic stability of these cycles.Comment: 34 pp., 4 tables, 30 references. Submitted to Nonlinearit

Multiple calcium binding sites make calmodulin multifunctional

Protein-protein or protein-ion interactions with multisite proteins are essential to the regulation of intracellular and extracellular events. There is, however, limited understanding of how ligand-multisite protein interactions selectively regulate the activities of multiple protein targets. In this paper, we focus on the important calcium (Ca2+) binding protein calmodulin (CaM), which has four Ca2+ ion binding sites and regulates the activity of over 30 other proteins. Recent progress in structural studies has led to significant improvements in the understanding of Ca2+-CaM- dependent regulation mechanisms. However, no quantitative model is currently available that can fully explain how the structural diversity of protein interaction surfaces leads to selective activation of protein targets. In this paper, we analyze the multisite protein-ligand binding mechanism using mathematical modelling and experimental data for Ca2+-CaM-dependent protein targets. Our study suggests a potential mechanism for selective and differential activation of Ca2+-CaM targets by the same CaM molecules, which are involved in a variety of intracellular functions. The close agreement between model predictions and experimental dose-response curves for CaM targets available in the literature suggests that such activation is due to the selective activity of CaM conformations in complexes with variable numbers of Ca2+ ions. Although the paper focuses on the Ca2+-CaM pair as a particularly data rich example, the proposed model predictions are quite general and can easily be extended to other multisite proteins. The results of the study may therefore be proposed as a general explanation for multifunctional target regulation by multisite proteins. © The Royal Society of Chemistry

Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are universal intracellular messengers whose concentrations are regulated by molecular networks comprised of different isoforms of the synthases adenylate cyclase or guanylate cyclase and the phosphodiesterases which degrade these compounds. In this paper, we employ a systems biology approach to develop mathematical models of these networks that, for the first time, take into account the different biochemical properties of the isoforms involved. To investigate the mechanisms underlying the joint regulation of cAMP and cGMP, we apply our models to analyse the regulation of cilia beat frequency in Paramecium by Ca2+. Based on our analysis of these models, we propose that the diversity of isoform combinations that occurs in living cells provides an explanation for the huge variety of intracellular processes that are dependent on these networks. The inclusion of both G-protein receptor and Ca 2+-dependent regulation of AC in our models allows us to propose a new explanation for the switching properties of G-protein subunits involved in nucleotide regulation. Analysis of the models suggests that, depending on whether the G-protein subunit is bound to AC, Ca2+ can either activate or inhibit AC in a concentration-dependent manner. The resulting analysis provides an explanation for previous experimental results that showed that alterations in Ca2+ concentrations can either increase or decrease cilia beat frequency over particular Ca2+ concentration ranges. © The Royal Society of Chemistry

Computational modelling suggests dynamic interactions between Ca ²⁺, IP<inf>3</inf> and G protein-coupled modules are key to robust Dictyostelium aggregation

Under conditions of starvation, Dictyostelium cells begin a programme of development during which they aggregate to form a multicellular structure by chemotaxis, guided by propagating waves of cyclic AMP that are relayed robustly from cell to cell. In this paper, we develop and analyse a new model for the intracellular and extracellular cAMP dependent processes that regulate Dictyostelium migration. The model allows, for the first time, a quantitative analysis of the dynamic interactions between calcium, IP3 and G protein-dependent modules that are shown to be key to the generation of robust cAMP oscillations in Dictyostelium cells. The model provides a mechanistic explanation for the transient increase in cytosolic free Ca2+ concentration seen in recent experiments with the application of the calmodulin inhibitor calmidazolium (R24571) to Dictyostelium cells, and also allows elucidation of the effects of varying both the conductivity of stretch-activated channels and the concentration of external phosphodiesterase on the oscillatory regime of an individual cell. A rigorous analysis of the robustness of the new model shows that interactions between the different modules significantly reduce the sensitivity of the resulting cAMP oscillations to variations in the kinetics of different Dictyostelium cells, an essential requirement for the generation of the spatially and temporally synchronised chemoattractant cAMP waves that guide Dictyostelium aggregation. © The Royal Society of Chemistry 2009