Functional domains of the human epididymal protease inhibitor, eppin

Eppin has two potential protease inhibitory domains: a whey acid protein or four disulfide core domain and a Kunitz domain. The protein is also reported to have antibacterial activity against Gram-negative bacteria. Eppin and its whey acid protein and Kunitz domains were expressed in Escherichia coli and their ability to inhibit proteases and kill bacteria compared. The Kunitz domain inhibits elastase (EC 3.4.21.37) to a similar extent as intact eppin, whereas the whey acid protein domain has no such activity. None of these fragments inhibits trypsin (EC 3.4.21.4) or chymotrypsin (EC 3.4.21.1) at the concentrations tested. In a colony forming unit assay, both domains have some antibacterial activity against E. coli, but this was not to the same degree as intact eppin or the two domains together. When bacterial respiratory electron transport was measured using a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, eppin and its domains caused an increase in the rate of respiration. This suggests that the mechanism of cell killing may be partly through the permeablization of the bacterial inner membrane, resulting in uncoupling of respiratory electron transport and consequent collapse of the proton motive force. Thus, we conclude that although both of eppin’s domains are involved in the protein’s antibacterial activity, only the Kunitz domain is required for selective protease inhibition.

An Innovative Model for the Provision of Practice Learning Opportunities in Family and Child Care: Newry Student Unit, Southern Health and Social Care Trust.

This article describes the work of Newry Student Unit which operates in the Southern Health and Social Care Trust. The background to the unit is outlined and its development is discussed in the context of practice learning provision in Northern Ireland. The operation of the unit in providing Family and Child Care practice learning opportunities (PLOs) for student social workers is outlined and findings from evaluation questionnaires completed by students, college tutors and team leaders are presented. The paper highlights both the advantages and disadvantages of this model of PLO provision and concludes that it is a valuable resource for practice learning. Proposals for the development of the unit are discussed and it is suggested that the model has the potential be replicated in other areas of Northern Ireland.

A topological algorithm for identification of structural domains of proteins

Background: Identification of the structural domains of proteins is important for our understanding of the organizational principles and mechanisms of protein folding, and for insights into protein function and evolution. Algorithmic methods of dissecting protein of known structure into domains developed so far are based on an examination of multiple geometrical, physical and topological features. Successful as many of these approaches are, they employ a lot of heuristics, and it is not clear whether they illuminate any deep underlying principles of protein domain organization. Other well-performing domain dissection methods rely on comparative sequence analysis. These methods are applicable to sequences with known and unknown structure alike, and their success highlights a fundamental principle of protein modularity, but this does not directly improve our understanding of protein spatial structure.

Exploring Innovative Methodologies in time and place to analyze child protection documents as elements of practice

This paper aims to demonstrate how a derived approach to case file analysis, influenced by the work of Michel Foucault and Dorothy E.Smith, can offer innovative means by which to study the relations between discourse and practices in child welfare. The article explores text-based forms of organization in histories of child protection in Finland and in Northern Ireland. It is focused on case file records in different organizational child protection contexts in two jurisdictions. Building on a previous article (Author 1 & 2: 2011), we attempt to demonstrate the potential of how the relations between practices and discourses –a majorly important theme for understanding child welfare social work – can be effectively analysed using a combination of two approaches This article is based on three different empirical studies from our two jurisdictions Northern Ireland (UK) and Finland; one study used Foucault; the other Smith and the third study sought to combine the methods. This article seeks to report on ongoing work in developing, for child welfare studies, ‘a history that speaks back’ as we have described it.

Distinct functional domains of the Salmonella enterica WbaP transferase that is involved in the initiation reaction for synthesis of the O antigen subunit

WbaP is a membrane enzyme that initiates O antigen synthesis in Salmonella enterica by catalysing the transfer of galactose 1-phosphate (Gal-1-P) onto undecaprenyl phosphate (Und-P). WbaP possesses at least three predicted structural domains: an N-terminal region containing four transmembrane helices, a large central periplasmic loop, and a C-terminal domain containing the last transmembrane helix and a large cytoplasmic tail. In this work, we investigated the contribution of each region to WbaP function by constructing a series of mutant WbaP proteins and using them to complement O antigen synthesis in DeltawbaP mutants of S. enterica serovars Typhi and Typhimurium. Truncated forms of WbaP lacking the periplasmic loop exhibited altered chain-length distributions in O antigen polymerization, suggesting that this central domain is involved in modulating the chain-length distribution of the O polysaccharide. The N-terminal and periplasmic domains were dispensable for complementation of O antigen synthesis in vivo, suggesting that the C-terminal domain carries the sugar-phosphate transferase activity. However, despite the fact that they complemented the synthesis of O antigen in the DeltawbaP mutant in vivo, membrane extracts containing WbaP derivatives without the N-terminal domain failed to transfer radioactive Gal from UDP-Gal into a lipid-rich fraction. These results suggest that the N-terminal region of WbaP, which contains four transmembrane domains, is essential for the insertion or stability of the protein in the bacterial membrane. We propose that the domain structure of WbaP enables this protein not only to function in the transfer of Gal-1-P to Und-P but also to establish critical interactions with additional proteins required for the correct assembly of O antigen in S. enterica.

Molecular modeling of N-terminal domains of NMDA-receptor. Study of ligand binding with N-terminal domains

Using the molecular-graphic complex Sybyl6.7.2, computational construction of spatial models for N-terminal domains (of NR1- and NR2B-subunits) of NMDA-receptor was conducted. On the basis of the constructed models and also CoMFA method the conclusion is made about presence of the binding site for the compounds similar to iphenprodyl in two N-terminal domains of NR1- and NR2B-subunits. The obtained data can be used for constructing new ligands.

‘Reforming Social Work Education: Some Reflections on the Contribution of Practice Learning’

Social work in the UK is currently undergoing a process of major reform and a wide range of recommendations have been made aimed at improving practice and education. This paper focuses on the Social Work Reform Board's proposals for improving practice learning in qualifying level social work education. It examines how recommendations for better partnership working between Higher Education Institutions and employers and developing critical reflection in agencies are likely to impact on student learning. Drawing on experience of social work education in Northern Ireland it considers the potential of the Reform Board's proposals for improving the quality of practice learning and enhancing students' preparedness for employment. The paper concludes that differences in educational aims and priorities, resistant practice cultures and cut-backs in resourcing could present major obstacles that must be overcome if this potential is to be realised.