Unexpected role of surface transglutaminase type II in celiac disease

Background & Aims: In celiac disease (CD), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. Methods: Duodenal biopsy specimens from 30 treated patients with CD, 33 untreated patients with CD, and 24 controls were cultured with or without gliadin peptides p31-43, pα-9, and deamidated pα-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with CD and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. Results: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. Conclusions: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of CD suggesting a third role for TG2 in CD. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases. © 2005 by the American Gastroenterological Association.

Public administration in an age of austerity:the future of the discipline

Reflecting changes in the nature of governance, some have questioned whether Public Administration is now an historical anachronism. While a legitimate debate exists between sceptics and optimists, this special issue demonstrates grounds for optimism by indicating the continuing diversity and adaptability of the field of Public Administration. In this introduction, we first sketch the variety of intellectual traditions which comprise the field of modern Public Administration. We then consider institutional challenges facing the subject given considerable pressures towards disciplinary fragmentation, and ideological challenges arising from a new distrust of public provision in the UK. Despite these challenges, Public Administration continues to provide a framework to analyse the practice of government and governance, governing institutions and traditions, and their wider sociological context. It can also directly inform policy reform - even if this endeavour can have its own pitfalls and pratfalls for the 'engaged' academic. We further suggest that, rather than lacking theoretical rigour, new approaches are developing that recognise the structural and political nature of the determinants of public administration. Finally, we highlight the richness of modern comparative work in Public Administration. Researchers can usefully look beyond the Atlantic relationship for theoretical enhancement and also consider more seriously the recursive and complex nature of international pressures on public administration. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The central role of the neutrophil in ischaemic/reperfusion injury

Inadequate blood flow to an organ, ischaemia, may lead to both local and remote tissue injury characterized by oedema, increased microvascular permeability to protein and degradation of connective tissue components. This damage is probably caused by the accumulation and inappropriate activation of neutrophils which occurs when the tissue is reperfused. To test this hypothesis a number of in vitro models of the sequential stages of ischaemia/reperfusion injury were examined. Methods were initially developed to examine the adhesion of neutrophils to monolayers of a cultured endothelial cell line (ECV304) after periods of hypoxia and reoxygenation. Neutrophil migration in response to factors secreted by the treated endothelial cells was then assessed. The genesis of an inappropriate oxidative burst by the neutrophil upon exposure to endothelial chemoattractants and adhesion molecules was also measured. Finally to appraise how tissue function might be affected by endothelial cell hypoxia the contractility of vascular smooth muscle was examined. Neutrophil adhesion to ECV304 cells, which had been hypoxic for 4 hours and then reoxygenated for 30 minutes, was significantly increased. This response was probably initiated by reactive oxygen species (ROS) generated by the endothelial cells. Blockage of their production by allopurinol reduced the heightened adhesion. Similarly removal of ROS by superoxide dismutase or catalase also attenuated adhesion. ROS generation in turn caused the release of a soluble factor (s) which induced a conformational change on the neutrophil surface allowing it to bind to the intercellular adhesion molecule 1 (ICAM-1) on the endothelial cell. Soluble factor (s) from hypoxia/reoxygenated endothelial cells also had a powerful neutrophil chemoattractant ability. When neutrophils were exposed to both hypoxic/reoxygenated endothelial cells and the soluble factor (s) released by them a large oxidative burst was elicited. This response was greatest immediately after reoxygenation and one hour later was diminishing suggesting at least one of the components involved was labile. Analysis of the supernatant from hypoxic/reoxygenated endothelial cell cultures and studies using inhibitors of secretion suggested platelet activating factor (PAF) may be a major component in this overall sequence of events. Lesser roles for IL-8, TNF and LTB4 were also suggested. The secretory products from hypoxia/reoxygenated endothelial cells also affected smooth muscle contractility having an anti-vasoconstrictor or relaxation property, similar to that exerted by PAF.

Lipophilic antifolates as potential antipsoriatic agents

The lipophilic dihydrofolate reductase (DHFR) inhibitor m-azidopyrimethamine (MZP) was investigated for suitability for development as a topical antipsoriatic agent. The clinical features and treatments for psoriasis were reviewed. High performance liquid chromatography (HPLC) was employed as the main analytical method, with UV spectroscopy being used in some cases. Reduction of the azido-group was proposed as a potential detoxification mechanism for MZP. The rates of reduction of a series of substituted phenyl azide compounds by dithiothreitol were investigated and found to depend on the substitution pattern of the aryl azide molecular, with electron deficient azides exhibiting faster rates of reduction in the system studied. The rates of reduction of MZP and analogous compounds were also studied using this model. The skin penetration of MZP was assessed using an in vitro hairless mouse skin model. The rate of permeation (flux) of MZP across hairless mouse skin was found to be dependent on the quantity of propylene glycol used as cosolvent in the vehicle and the pH. The use of a pretreatment regime of oleic acid in propylene glycol was shown to greatly increase the penetration of MZP through the hairless mouse skin as compared to application without pretreatment, or pretreatment with other penetration enhancers. The metabolism of MZP was studied in in vitro models comprising skin homogenates, SV-K14 human keratinocyte cell cultures and skin commensal bacterial cultures. No conversion of MZP to the corresponding amine was detected in any of the models. The growth inhibitory properties of MZP were investigated in an in vitro SV-K14 human keratinocyte cell culture model and compared with those of other DHFR inhibitors. [14C]-pyrimethamine was shown to be taken up by the SV-K14 keratinocytes.

Manufacturing organisation in developing countries with particular reference to Iraq

Industrially developed countries are able to absorb modern techniques of science and technology quite readily; this is not the case for less-developed countries. Attempts made by developing countries have been ineffective due to factors not readily admitted. This thesis highlights the areas that need to be developed by under-developed countries, and covers economic, scientific and technological, and social aspects as well as technology transfer. Economic areas considered acknowledge that within any one country there should be proper procedures for planning economic and industrial projects (plant design) supported by efficient economic development strategy. Scientific and technological factors considered include the major areas that need to be developed in order to produce and/or deal with scientific and technological issues for the interest of the national development. Technology transfer areas considered include the necessity of building up a national body (system) responsible for dealing with activities and tasks of transferring foreign-made technology so that it can be employed effectively within the environment of the country. Social factors considered include the need to develop human resources which can be employed efficiently into the whole process of development, and particularly for the above proposed systems. Education and training are the major elements that ought to be tackled to produce skilled manpower and to overcome the social and cultural values and traditions that are inherited by the society. This thesis highlights the above areas in an attempt to plan and organise the development of science and technology, and their implementation into the development as a whole. Whilst recognising the problems of creating this sort of development in developing countries, the author considers the benefits to be obtained are much greater in the long run.

Understanding sustainable development

Sustainable development is notoriously difficult to grasp for students and professionals. Multidimensional, encompassing social, ecological and economic theories, policies and practice, it can be a maze of complexity and contradiction. This powerful new textbook, by a topic instructor in the field, is the first to unravel sustainable development and provide readers with the deep understanding so often missing in other texts. The book adopts a multi-perspective approach designed specifically to allow access to the topic from a wide range of educational and professional backgrounds and to develop understanding of a diversity of approaches and traditions at different levels. It features multiple entry points, explains jargon and explores controversies. Also offering boxed examples from the local to the global, Understanding Sustainable Development is the most complete guide to the subject for course leaders, students and self-learners.

Unknown agents in translated political discourse

This article investigates the role of translation and interpreting in political discourse. It illustrates discursive events in the domain of politics and the resulting discourse types, such as jointly produced texts, press conferences and speeches. It shows that methods of Critical Discourse Analysis can be used effectively to reveal translation and interpreting strategies as well as transformations that occur in recontextualisation processes across languages, cultures, and discourse domains, in particular recontextualisation in mass media. It argues that the complexity of translational activities in the field of politics has not yet seen sufficient attention within Translation Studies. The article concludes by outlining a research programme for investigating political discourse in translation. ©2012 John Benjamins Publishing Company.

A cross-culture, cross-gender comparison of perspective taking mechanisms

Being able to judge another person's visuo-spatial perspective is an essential social skill, hence we investigated the generalizability of the involved mechanisms across cultures and genders. Developmental, cross-species, and our own previous research suggest that two different forms of perspective taking can be distinguished, which are subserved by two distinct mechanisms. The simpler form relies on inferring another's line-of-sight, whereas the more complex form depends on embodied transformation into the other's orientation in form of a simulated body rotation. Our current results suggest that, in principle, the same basic mechanisms are employed by males and females in both, East-Asian (EA; Chinese) and Western culture. However, we also confirmed the hypothesis that Westerners show an egocentric bias, whereas EAs reveal an other-oriented bias. Furthermore, Westerners were slower overall than EAs and showed stronger gender differences in speed and depth of embodied processing. Our findings substantiate differences and communalities in social cognition mechanisms across genders and two cultures and suggest that cultural evolution or transmission should take gender as a modulating variable into account.

How does knowledge relate to political action?

In this paper we investigate the relation between knowledge and political action, focusing on knowledge claims stemming from science that at the same time have relevance in a policy context. In so doing, we will revisit some well-known and some lesser known approaches, such as C.P. Snow's thesis of the two cultures and Mannheim's conceptualization of theory and practice. We arrive at a distinction between knowledge for practice and practical knowledge, which we briefly apply to the case of climate change science and policy. We state as our thesis that policy is ever more reliant on knowledge, but science can deliver ever less certainty. Political decisions and programs have to recognize this fact, either implicitly or explicitly. This creates a paradox that is normally resolved through the political decision and not the dissemination of "truth" in the sense of uncontested knowledge. We use the case of the Intergovernmental Panel on Climate Change as an example. © 2012 Copyright ICCR Foundation.

Understanding sustainable development

This new and expanded edition builds upon the first edition’s powerful multi-perspective approach and breath of coverage. A truly comprehensive introduction to sustainable development, it is designed specifically to allow access to the topic from a wide range of educational and professional backgrounds and to develop understanding of a diversity of approaches and traditions at different levels. This second edition includes: •a complete update of the text, with increased coverage of major topics including ecosystems; production and consumption; business; urban sustainability; governance; new media technologies; conservation; leadership; globalization and global crises; sustainability literacy and learning; •more examples from the Global South and North America, while retaining its unique coverage of first world countries; •chapter aims at the start and summaries at the end of each chapter; •glossary of key terms; •a new chapter on Conservation with a focus on behaviour change and values; •a brand new website which includes discussion of how projects are done on the ground, additional exercises and online cases, test questions and recommended readings and films. Offering boxed examples from the local to the global, Understanding Sustainable Development is the most complete guide to the subject for course leaders, undergraduates and postgraduates.

Assessing learning in Higher Education

Assessing Learning in Higher Education addresses what is probably the most time-consuming part of the work of staff in higher education, and something to the complexity of which many of the recent developments in higher education have added. Getting assessment ‘right’– that is, designing and implementing appropriate models and methods, can determine the future lives and careers of students. But, as Professor Phil Race comments in his excellent and thought-provoking foreword, students entering higher education often have little idea about how exactly assessment will work, and often find that the process is very different from anything they have previously encountered. Assessing Learning in Higher Education contains innovative approaches to assessment drawn from many different cultures and disciplines. The chapter authors argue the need for changing assessment and feedback processes so that they embrace online collaboration and discussion between students as well as between ‘students’ and ‘faculty’. The chapters demonstrate that at some points there is a need to be able to measure individual achievement, and to do this in ways that are valid, transparent, authentic – and above all fair. Assessment and feedback processes need to ensure that students are well prepared for this individual assessment, but also to take account of collaboration and interaction. The respective chapters of Assessing Learning in Higher Education all of which are complete in themselves, but with very useful links to ideas in other chapters, provide numerous illustrations of how this can be achieved.

Reaching for The Top, Second edition

An overview of FLorida International University 's plans, strategies, goals, and traditions emphasizing University growth and performance.

A case study of a liberal Jewish day school's middle school transition

The Jacobson Sinai Academy is a Liberal Reform Jewish Day School, in North Miami Beach, Florida. When the Academy was started over 18 years ago it was designed as a K–6 school. This was in keeping with the existing model for Reform day schools at the time and met the needs and desires of the early founders. The philosophy of the school addressed meeting the needs of the individual child as well as the fostering of Judaic values and traditions in an academically nurturing and experiential setting. Upon graduation, students moved from the Academy to a variety of public and private options, all of which served the needs of the families at the time. In recent years, due to numerous factors within the community, parents voiced concerns as to where their children would continue their education during the critical middle school years. As a result of these concerns, and through the efforts of a dedicated group of parents and lay leaders, the decision was made to add an upper school component to the existing elementary configuration. This study is a qualitative case study which chronicles the organizational change effort that was undertaken for this purpose to determine facilitating conditions and impediments leading to the change. The analysis serves to inform others wishing to advance such an undertaking. ^ Results of the study indicated that certain conditions are necessary for the successful implementation of any change effort. The culture of the organization must be acknowledged and is a primary factor to be considered when advancing change. Collaboration with those committed to the enterprise must occur, and this in turn can lead to an agreed upon philosophy which expresses the diversity of needs and values of all of those involved. Resistance, while expected from certain individuals within the organization, can be overcome through the efforts of key players who assume leadership positions that are transformational in nature. Additionally, the rationale for middle schools, and the need for this one in particular, are factors which led to the success of this initiative. ^

Administrators' perspectives of culture at a multicampus community college

The purpose of this study was to explore how administrators’ perceived the campus and administrative cultures found on a single campus of a multicampus community college system. A review of the literature revealed that the culture found in higher education institutions contains a high degree of human interactions, has a myriad of cultures, and that individuals play a significant role in the maintenance or the evolution of the cultures present. The study site was Neighborhood Campus which is one campus of a large urban community college system containing a total of eight campuses, Urban College. Kuh’s conventional organizational models served to identify the model on Neighborhood Campus, Levin’s cultural definitions described the campus culture, and cultural definitions from Bergquist and Pawlak formed the framework for the administrative culture. The study was guided by the following research questions: What are the administrators’ perspectives of the campus culture on a community college campus and what are the administrators’ perspectives of the administrative culture on a community college campus? A qualitative case study method was used, data collection included interviews, document and videograph reviews, and observations of administrative meetings. The participants for the interview portion of the study included 10 individuals defined as administrators. ^ The study revealed that administrators’ perspectives of these cultures demonstrated five themes (student-centered, size, location, Hispanics, and family) served as contributors to the campus culture. The administrative culture was supported by six themes (size, team, collaboration, open, Inclusion, and rewards and recognition). ^ The findings revealed three of Kuh’s conventional organizational models (rational, bureaucratic, and collegial models) were seen as being in place at Neighborhood Campus. Levin’s traditional and service cultures were seen in the campus culture with the service culture demonstrating dominance. Using Bergquist and Pawlak’s definitions, components of the collegial, managerial, and developmental cultures appear to be present in the administrative culture with the collegial culture serving as the dominant administrative culture. ^ Through an understanding of these cultures and themes, administrators can provide leadership that is sensitive to these cultures, especially if institutional change is required.^

World-Class Service

In the discussion - World-Class Service - by W. Gerald Glover, Associate Professor, Restaurant, Hotel and Resort Management at Appalachian State University and Germaine W. Shames, Hilton International, New York, Glover and Shames initially state: “Providing world-class service to today's traveler may be the key for hospitality managers in the current competitive market. Although an ideal, this type of service provides a mandate for culturally aware managers. The authors provide insight into several areas of cultures in collision.” Up to the time this essay is written, the authors point to a less-than-ideal level of service as being the standard in the hospitality industry and experience. “Let's face it - if we're ever to resurrect service, it will not be by going back to anything,” Glover and Shames exclaim. “Whatever it was we did back then has contributed to the dilemma in which we find ourselves today, handicapped by a reactive service culture in an age that calls for adaptiveness and global strategies,” the authors fortify that thought. In amplifying the concept of world-class service Glover and Shames elaborate: “World-class service is an ideal. Proactive and adaptive, world-class service feels equally right to the North American dignitary occupying the Presidential Suite, and the Japanese tourist staying in a standard room in the same hotel.” To bracket that model the authors offer: “At a minimum, it is service perceived by each customer as appropriate and adequate. At its best, it may also make the customer feel at home, among friends, or pampered. Finally, it is service as if culture matters,” Glover and Shames expand and capture the rule of world-class service. Glover and Shames consider the link between cultures and service an imperative one. They say it is a principle lost on most hospitality managers. “Most [managers] have received service management education in the people are people school that teaches us to disregard cultural differences and assume that everyone we manage or serve is pretty much like ourselves,” say Glover and Shames. “Is it any wonder that we persist in setting service standards, marketing services, and managing service staff not only as if culture didn't matter, but as if it didn't exist?!” To offer legitimacy to their effort Glover and Shames present the case of the Sun and Sea Hotel, a 500-room first class hotel located on the outskirts of the capital city of a small Caribbean island nation. It is a bit difficult to tell whether this is a dramatization or a reality. It does, however, serve to illustrate their point in regard to management’s cognizance, or lack thereof, of culture when it comes to cordial service and guest satisfaction. Even more apropos is the tale of the Palace Hotel, “…one of the grande dames of hospitality constructed in the boom years of the 1920s in a mid-sized Midwestern city in the United States.” The authors relate what transpired during its takeover in mid-1980 by a U.S.-based international hotel corporation. The story makes for an interesting and informative case study.