Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice

Genetic or vitamin D3-induced overexpression of thymic stromal lymphopoietin (TSLP) by keratinocytes results in an atopic dermatitis (AD)-like inflammatory phenotype in mice echoing the discovery of high TSLP expression in epidermis from AD patients. Although skin dendritic cells (DC) are suspected to be involved in AD, direct evidence of a pathogenetic role for skin DC in TSLP-induced skin inflammation has not yet been demonstrated. In a mouse model of AD, i.e. mice treated with the low-calcemic vitamin D3 analogue, MC903, we show that epidermal Langerhans cells (LC)-depleted mice treated with MC903 do neither develop AD-like inflammation nor increased serum IgE as compared to vitamin D3 analogue-treated control mice. Accordingly, we show that, in mice treated with MC903 or in K14-TSLP transgenic mice, expression of maturation markers by LC is increased whereas maturation of dermal DC is not altered. Moreover, only LC are responsible for the polarization of naive CD4+ T cells to a Th2 phenotype, i.e. decrease in interferon-gamma and increase in interleukin (IL)-13 production by CD4+ T cells. This effect of LC on T-lymphocytes does not require OX40-L/CD134 and is mediated by a concomitant down-regulation of IL-12 and CD70. Although it was previously stated that TSLP up-regulates the production of thymus and activation-regulated chemokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) and macrophage-derived chemokine (MDC)/CCL22 by human LC in vitro, our work shows that production of these Th2- cell attracting chemokines is increased only in keratinocytes in response to TSLP overexpression. These results demonstrate that LC are required for the development of AD in mouse models of AD involving epidermal TSLP overexpression.

Prising open the black box: Critical realism, action research and social work

There is a growing interest in critical realism and its application to social work. This article makes a case for adopting this philosophical position in qualitative social work research. More specifically, it suggests that there is a concordance between critical realist premises and action research with its cyclical inquiry and advancement of social change. This combination of philosophy and method, it is argued, promotes anti-oppressive social work research and illuminates the processes shaping outcomes in programme evaluations. Overall, the article underscores the importance of 'depth' in qualitative inquiry by conceiving the social world in terms of five interlacing, social domains.

Specific growth rate plays a critical role in hydrogen peroxide resistance of the marine oligotrophic ultramicrobacterium Sphingomonas alaskensis strain RB2256

The marine oligotrophic ultramicrobacterium Sphingomonas alaskensis RB2256 has a physiology that is distinctly different from that of typical copiotrophic marine bacteria, such as Vibrio angustum S14. This includes a high level of inherent stress resistance and the absence of starvation-induced stress resistance to hydrogen peroxide. In addition to periods of starvation in the ocean, slow nutrient-limited growth is likely to be encountered by oligotrophic bacteria for substantial periods of time. In this study we examined the effects of growth rate on the resistance of S. alaskensis RB2256 to hydrogen peroxide under carbon or nitrogen limitation conditions in nutrient-limited chemostats. Glucose-limited cultures of S. alaskensis RB2256 at a specific growth rate of 0.02 to 0.13 h(-1) exhibited 10,000-fold-greater viability following 60 min of exposure to 25 mM hydrogen peroxide than tells growing at a rate of 0.14 h(-1) or higher. Growth rate control of stress resistance was found to be specific to carbon and energy limitation in this organism. In contrast, V. angustum S14 did not exhibit growth rate-dependent stress resistance. The dramatic switch in stress resistance that was observed under carbon and energy limitation conditions has not been described previously in bacteria and thus may be a characteristic of the oligotrophic ultramicrobacterium, Catalase activity varied marginally and did not correlate with the growth rate, indicating that hydrogen peroxide breakdown was not the primary mechanism of resistance. More than 1,000 spots were resolved on silver-stained protein gels for cultures growing at rates of 0.026, 0.076, and 0.18 h(-1). Twelve protein spots had intensities that varied by more than twofold between growth rates and hence are likely to be important for growth rate-dependent stress resistance. These studies demonstrated the crucial role that nutrient limitation plays in the physiology of S. alaskensis RB2256, especially under oxidative stress conditions.

An elasto-plastic critical state framework for unsaturated soil.

Data from a series of controlled suction triaxial tests on samples of compacted speswhite kaolin were used in the development of an elasto–plastic critical state framework for unsaturated soil. The framework is defined in terms of four state variables: mean net stress, deviator stress, suction and specific volume. Included within the proposed framework are an isotropic normal compression hyperline, a critical state hyperline and a state boundary hypersurface. For states that lie inside the state boundary hypersurface the soil behaviour is assumed to be elastic, with movement over the state boundary hypersurface corresponding to expansion of a yield surface in stress space. The pattern of swelling and collapse observed during wetting, the elastic–plastic compression behaviour during isotropic loading and the increase of shear strength with suction were all related to the shape of the yield surface and the hardening law defined by the form of the state boundary. By assuming that constant–suction cross–sections of the yield surface were elliptical it was possible to predict test paths for different types of triaxial shear test that showed good agreement with observed behaviour. The development of shear strain was also predicted with reasonable success, by assuming an associated flow rule.

A critical review of some recent developments in quantitative research on gender and achievement in the United Kingdom

Over recent years the findings of a number of quantitative research studies have been published in the UK on gender and achievement. Much of this work has emanated from Stephen Gorard and his colleagues and has not only been highly critical of existing approaches to handling quantitative data but has also suggested a number of alternative and, what they claim to be, more valid ways of measuring differential patterns of achievement and underachievement between groups. This article shows how much of this work has been based upon rather under-developed measures of achievement and underachievement that tend, in turn, to generate a number of misleading findings that have questionable implications for practice. It will be argued that this body of work provides a useful case study in the problems of quantitative research that fails to engage adequately with the substantive theoretical and empirical literature and considers some of the implications of this for future research in this area.

Critical reading of science-based news reports: Establishing a knowledge skills and attitudes framework

A recognised aim of science education is to promote critical engagement with science in the media. Evidence would suggest that this is challenging for both teachers and pupils and that at science education does not yet adequately prepare young people for this task. Furthermore, in the absence of clear guidance as to what this means and how this may be achieved it is difficult for teachers to develop approaches and resources that address the matter and that systematically promote such critical engagement within their teaching programmes. Twenty-six individuals with recognised expertise or interest in science in the media, drawn from a range of disciplines and areas of practice, constituted a specialist panel in this study. The question this research sought to answer was ‘what are the elements of knowledge, skill and attitude which underpin critical reading of science based news reports’? During in-depth individual interviews the panel were asked to explore what they considered to be essential elements of knowledge, skills and attitude which people need to enable them to respond critically to news reports with a science component. Analysis of the data revealed fourteen fundamental elements which together contribute to an individual’s capacity to engage critically with science-based news. These are classified in five categories ‘knowledge of science’, ‘knowledge of writing and language’, ‘knowledge about news, newspapers and journalism’, ‘skills’ and ‘attitudes’. Illustrative profiles of each category along with indicators of critical engagement are presented. The implications for curriculum planning and pedagogy are considered.