The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.Comment: Accepted for publication in BMC Systems Biology. 17 pages, 6 Figures, + supplementary informatio

An assertion language for constraint logic programs

In an advanced program development environment, such as that discussed in the introduction of this book, several tools may coexist which handle both the program and information on the program in different ways. Also, these tools may interact among themselves and with the user. Thus, the different tools and the user need some way to communicate. It is our design principie that such communication be performed in terms of assertions. Assertions are syntactic objects which allow expressing properties of programs. Several assertion languages have been used in the past in different contexts, mainly related to program debugging. In this chapter we propose a general language of assertions which is used in different tools for validation and debugging of constraint logic programs in the context of the DiSCiPl project. The assertion language proposed is parametric w.r.t. the particular constraint domain and properties of interest being used in each different tool. The language proposed is quite general in that it poses few restrictions on the kind of properties which may be expressed. We believe the assertion language we propose is of practical relevance and appropriate for the different uses required in the tools considered

Academic achievement : the role of praise in motivating students

The motivation of students is an important issue in higher education, particularly in the context of the increasing diversity of student populations. A social-cognitive perspective assumes motivation to be dynamic, context-sensitive and changeable, thereby rendering it to be a much more differentiated construct than previously understood. This complexity may be perplexing to tutors who are keen to develop applications to improve academic achievement. One application that is within the control of the tutor, at least to some extent, is the use of praise. Using psychological literature the article argues that in motivating students, the tutor is not well served by relying on simplistic and common sense understandings of the construct of praise and that effective applications of praise are mediated by students' goal orientations, which of themselves may be either additive or interactive composites of different objectives and different contexts

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Trust and Credibility in Web-Based Health Information: A Review and Agenda for Future Research

Background: Online sources are becoming increasingly important in health information seeking, such that they may have a significant effect on health care decisions and outcomes. Hence, given the wide range of different sources of online health information from different organisations and individuals, it is important to understand how information seekers evaluate and select the sources that they use, and, more specifically how they assess their credibility and trustworthiness. Objectives: This article reviews empirical studies on trust and credibility in the use of online health information. The article seeks to present a profile of the research conducted on trust and credibility in online health information seeking, to identify the factors that impact judgements of trustworthiness and credibility, and to explore the role of demographic factors affecting trust formation. On this basis, it aims to identify the gaps in current knowledge and to propose an agenda for future research. Methods: A systematic literature review was conducted. Searches were conducted using a variety of combinations of the terms: online health information, trust, credibility, and their variants, in four multi-disciplinary and four health-oriented databases. Articles selected were published in English from 2000 onwards; this process generated 3827 unique records. After the application of exclusion criteria, this was reduced to a final dataset of 73 articles, which was analysed in full. Results: Interest in this topic has persisted over the last 15 years, with articles being published in medicine, social science and computer science, and focussing mostly on the USA and the UK. Documents in the dataset fell into three categories: those using trust or credibility as a dependent variable, those using trust or credibility as an independent variable, and studies of the demographic factors that influence the role of trust or credibility in online health information seeking. There is a consensus that in terms of website design, clear layout and design, interactive features and the authority of the owner have a positive effect on trust or credibility, whilst advertising has a negative effect. With regard to content features, authority of the author, ease of use and content have a positive effect on trust or credibility formation. Demographic factors influencing trust formation are age, gender and perceived health status. Conclusions: There is considerable scope for further research. This includes: increased clarity of the interaction between the variables associated with health information seeking; increased consistency on the measurement of trust and credibility; a greater focus on specific online health information sources; and, enhanced understanding of the impact of demographic variables on trust and credibility judgement

Using global analysis, partial specifications, and an extensible assertion language for program validation and debugging

We discuss a framework for the application of abstract interpretation as an aid during program development, rather than in the more traditional application of program optimization. Program validation and detection of errors is first performed statically by comparing (partial) specifications written in terms of assertions against information obtained from (global) static analysis of the program. The results of this process are expressed in the user assertion language. Assertions (or parts of assertions) which cannot be checked statically are translated into run-time tests. The framework allows the use of assertions to be optional. It also allows using very general properties in assertions, beyond the predefined set understandable by the static analyzer and including properties defined by user programs. We also report briefly on an implementation of the framework. The resulting tool generates and checks assertions for Prolog, CLP(R), and CHIP/CLP(fd) programs, and integrates compile-time and run-time checking in a uniform way. The tool allows using properties such as types, modes, non-failure, determinacy, and computational cost, and can treat modules separately, performing incremental analysis

Showing Israel the red card. Activists engaged in pro-Palestinian sport-related campaigns

© 2017 Informa UK Limited, trading as Taylor & Francis Group. This article explores the motivations of activists involved in pro-Palestinian sports-based campaigns. The activists’ intention is to bring pressure to bear upon Israel until it complies with international law and supports the rights of Palestinian people under the universal principles of human rights. In response to expressions of pro-Palestinian solidarity, the Israeli state and its supporters are interpreting such activity as a ‘new’ manifestation of ‘old’ antisemitism. In seeking to assess whether such activity is informed by antisemitism, 10 semi-structured interviews were conducted with activists to examine their motives. Their political biographies were explored as were their views on the use of sport as platform to express support for the Palestinian people and/or their displeasure at Israeli participation in international sport. One central theme was the activists’ responses to the suggestion that they were motivated by antisemitism. A qualitative content analysis of the interview transcripts revealed a shared observation that the accusation of antisemitism was a ‘shameless tactic’ employed by those seeking to cover up the ongoing injustices experienced by the Palestinian people. Sport was seen as a legitimate platform for political activity, to raise public awareness and to put pressure on the Israeli state. The findings contribute to a better understanding of activist motivations, the use of sport as a political platform and the challenges facing sport and its governing bodies

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left