A Dual Function for Prickle in Regulating Frizzled Stability during Feedback-Dependent Amplification of Planar Polarity

The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves. Despite intense efforts, the molecular pathways underlying feedback have proven difficult to elucidate using conventional genetic approaches. Here we investigate core protein function during planar polarization of the Drosophila wing by combining quantitative measurements of protein dynamics with loss-of-function genetics, mosaic analysis, and temporal control of gene expression. Focusing on the key core protein Frizzled, we show that its stable junctional localization is promoted by the core proteins Strabismus, Dishevelled, Prickle, and Diego. In particular, we show that the stabilizing function of Prickle on Frizzled requires Prickle activity in neighboring cells. Conversely, Prickle in the same cell has a destabilizing effect on Frizzled. This destabilizing activity is dependent on the presence of Dishevelled and blocked in the absence of Dynamin and Rab5 activity, suggesting an endocytic mechanism. Overall, our approach reveals for the first time essential in vivo stabilizing and destabilizing interactions of the core proteins required for self-organization of planar polarity

Deliberative and epistemic approaches to democracy

Deliberative and epistemic approaches to democracy are two important dimensions of contemporary democratic theory. This chapter studies these dimensions in the emerging ecosystem of civic and political participation tools, and appraises their collective value in a new distinct concept: linked democracy. Linked democracy is the distributed, technology-supported collective decision-making process, where data, information and knowledge are connected and shared by citizens online. Innovation and learning are two key elements of Athenian democracies which can be facilitated by the new digital technologies, and a cross-disciplinary research involving computational scientists and democratic theorists can lead to new theoretical insights of democracy

Comprehensive or Comprehensible Experience? A Case Study of Religion and Traumatic Bereavement

The first half of this article provides a brief overview of two respective projects concerning traumatic bereavement, in which religious faith appeared to feature amid a constellation of significant coping and sense-making mechanisms for survivors. After presenting some illustrative examples of the kind of data produced in the course of our research, the second half of the article develops a retrospectively critical appraisal of our data collection and corresponding analysis practices. In questioning the extent to which our accounts of our participants’ accounts can be considered adequate representations of social order, we critically explore the relative potential of ‘reflexivity’ for bridging the experiential gap between researchers and participants. Taken together, these reflections prompt a return to the salutary question: what counts as sociologically ‘see-able’

Using value of statistical life for the ex ante evaluation of transport policy options: a discussion based on ethical theory

This paper aims to discuss a number of questions that are highly important for the ex ante evaluation of the safety impacts of transport policy options, from the perspective of ethical theory: (1) Is it morally OK to express prevention on acceptance of fatalities or risks in monetary terms? (2) How useful is the concept of the value of a statistical life (VOSL) for ex ante evaluations of transport policy options? (3) What are the pros and cons of pricing protection of lives or prevention of risks in ex ante evaluations? (4) Which methods are available for expressing (protection of) human lives in monetary terms, and what are the main related methodological discussions? (5) Are all safety-related costs generally included in ex ante evaluations of the safety impacts of transport policy options, and if not: what is the relevance of excluded costs categories from an ethical perspective? (6) How important is the distribution of safety effects from an ethical perspective? The answer to the first question highly depends on the ethical theory that is used. With respect to question 2 we think that the VOSL is a useful concept, but that its application is not straightforward, for several reasons. Thirdly we think that probably pricing safety improves the quality of decision making, but to the best of our knowledge there is no research to underpin this expectation. The answer to question 4 is that several methods exist to estimate the value of a statistical life (VOSL), willingness-to-pay (WTP) methods being the most common category of methods. However, several methodological issues arise that make estimates of VOSL less straightforward. With respect to question 5 we conclude that behaviour-related avoidance costs are often overlooked and that these costs are relevant from an ethical perspective because the freedom to move and the freedom to participate in activities are challenged. Finally the answer to question 6 is that from an ethical perspective, in terms of the evaluation of policy measures, it might matter which groups of the population are the victims of the transport system, or are at risk. Egalitarian theories as well as sufficientarianism are useful theories to discuss distribution effects. Different theories conclude differently. © 2012 The Author(s)

Bacterial community assembly and turnover within the intestines of developing zebrafish

Background: The majority of animal associated microorganisms are present in digestive tract communities. These intestinal communities arise from selective pressures of the gut habitats as well as host’s genotype are regarded as an extra ‘organ’ regulate functions that have not evolved wholly on the host. They are functionally essential in providing nourishment, regulating epithelial development, and influencing immunity in the vertebrate host. As vertebrates are born free of microorganisms, what is poorly understood is how intestinal bacterial communities assemble and develop in conjunction with the development of the host. Methodology/Principal Findings: Set within an ecological framework, we investigated the bacterial community assembly and turnover within the intestinal habitats of developing zebrafish (from larvae to adult animals). Spatial and temporal species-richness relationships and Mantel and partial Mantel tests revealed that turnover was low and that richness and composition was best predicted by time and not intestinal volume (habitat size) or changes in food diet. We also observed that bacterial communities within the zebrafish intestines were deterministically assembled (reflected by the observed low turnover) switching to stochastic assembly in the later stages of zebrafish development. Conclusions/Significance: This study is of importance as it provides a novel insight into how intestinal bacterial communities assemble in tandem with the host’s development (from early to adult stages). It is our hope that by studying intestinal microbiota of this vertebrate model with such or some more refined approaches in the future could well provide ecological insights for clinical benefit. In addition, this study also adds to our still fledgling knowledge of how spatial and temporal species-richness relationships are shaped and provides further mounting evidence that bacterial community assembly and dynamics are shaped by both deterministic and stochastic considerations