Negotiating sacred roles:a sociological exploration of priests who are mothers

In 1992, in a historic move, the Church of England voted to allow women's ordination to priesthood and in 1994 the first women priests started to be ordained. Despite much research interest, the experiences of priests who are mothers to dependent children have been minimally investigated. Based on in-depth interviews with seventeen mothers ordained in the Church, this paper will focus on how the sacred-profane boundary is managed. Priests who are mothers have a particular insight into the Church hierarchy as they symbolically straddle the competing discourses of sacred and profane. However, instead of reifying these binaries, the experiences of these women show how such dualisms are challenged and managed in everyday life. Indeed, in terms of experience, ritual, ministry and preaching, priests who are mothers are resisting, recasting and renegotiating sacred terrain in subtle and nuanced ways. Mothers thus not only negotiate the practical and sacramental demands placed on priests, but also illuminate how the sacred domain is regulated and constructed.

Structure and regulation of type 2 transglutaminase in relation to its physiological functions and pathological roles

This chapter contains sections titled: Introduction Structure and Regulation Physiologic Functions of TG2 Disruption of TG2 Functions in Pathologic Conditions Perspectives for Pharmacologic Interventions Concluding Comments Acknowledgements References

The changing roles of production and operations managers in Britain from the 1970s to the 1990s

This article examines the careers and changing roles of British production and operations managers through three surveys covering the last quarter of the twentieth century. Careers are examined in terms of both their organisational context and the subjective experiences of those who have chosen this field, during a period of great turbulence for manufacturing due to growing global competition. The persistent features of such roles and responsibilities are contrasted with the changes in focus and demands. The managers' sources of satisfaction and frustration are outlined as are their perceptions of their situation in relation to managers in other areas. The article concludes by considering what has changed and what needs to change, in order for manufacturing to gain maximum benefit from the contribution of these managers.

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly Gq- and to a lesser extent Gs-mediated; p38 activation even had a small Gi-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

Customer orientation and innovativeness:differing roles in new and old Europe

Burgess and Steenkamp [Burgess, S. M., & Steenkamp, J. (2006). Marketing renaissance: How research in emerging markets advances marketing science and practice. International Journal of Research in Marketing, 23(4), 337-356.] have pointed out that marketing knowledge derives almost exclusively from research conducted in high income, industrialized countries. However, the generalizability of marketing knowledge should also be tested in emerging markets. We demonstrate that returns on customer orientation and organizational innovativeness play out differently in New versus Old Europe. Contrary to previous research, we find that customer focus is at least as important in New Europe as in our Old European country, while organizational innovativeness appears more important in New Europe to drive both customer service and financial performance.

A cross-national comparative study of the roles of men in contemporary France and Britain

The purpose of this thesis is to increase understanding and contribute to knowledge about the attitudes and behaviour of men in contemporary France and Britain. The thesis has three main aims: firstly, to provide the first cross-national comparison of French and British writing and research on the place of men in contemporary society; secondly, to identify similarities and differences in the roles of men in France and Britain; and thirdly, to determine to what extent and in what way such similarities and differences are linked to the social structures and cultural background of each country. The thesis focuses on two main facets of the male experience: the relationship between men and women and the interaction between fathers and their children. Men's attitudes and behaviour are examined in relation to issues such as the division of household tasks and child care within the family, parental roles, female employment, role reversal, gender stereotyping and changes towards a new image of masculinity in society. Particular consideration is given to differences in governmental attitudes in France and Britain towards the introduction of family policy measures for men as fathers. The thesis ends with a discussion of legislative, social and educational measures which could be introduced in France and Britain in order to promote greater flexibility in men's roles and consequently improve gender equality in each country. The data analysed in the thesis are derived from a questionnaire-based empirical study involving 101 men in Britain and seventy-five men in France. The respondents' experience of and attitudes towards their roles in society are analysed and interpreted in the light of profile data relating to their family circumstances and with reference to knowledge about the broader socio-cultural context.

The changing roles of accountants in industry.

Both accountants and their professional associations have come under pressure in recent years to move with a changing environment. A research project was established therefore in order to study the present roles of accountants in industry, to consider how such roles have evolved, and to consider ways in which these roles might change in the future. Apart from these specific objectives, the thesis also attempts to come to terms with some of the major philosophical and theoretical challenges that face sociology. Given these broad aims, and given a limited amount of previous research, the approach was to derive tentative classifications and propositions from empirical investigation, rather than to test preconceived hypotheses. Data was obtained primarily from ninety-nine structured interviews with both accountants and other managers from twelve industrial enterprises. Aside from studying specifically the changing roles of accountants in industry, the following areas were investigated: the historical development of industrial organisations, accounting systems, and the professional accounting bodies; the process of occupational entry, socialisation, and career paths of accountants; and the current education, training, and career development of, and labour market for, accountants in industry. Despite variations according to accountants' positions, the sample's work characteristics and orientations were found to be similar to those of managers from other areas. In fact most accountants were more concerned with 'getting on' than committed to a career in accounting or to any particular professional association or employing organisation. While there was a move towards a more general business involvement for the majority of the sample, there was also in some cases an increasing demand for specialist accounting skills. In conclusion, although an eventual technological substitution for the work of accountants in industry is thought to be unlikely, their work is becoming more liable to evaluation and intervention form those outside their occupational group.

Novel biological roles for pyrimidines

The development of classical and lipophilic inhibitors of dihydrofolate reductase (DHFR) as antitumour agents is reviewed and the advantages and problems associated with each class are discussed. The antitumour activity, pharmacokinetics and metabolism of m-azido-pyrimethamine (MZP), a novel lipophilic inhibitor, are considered and compared with metoprine, the prototype lipophilic antifolate. Evidence for a folate-independent target for lipophilic DHFR inhibitors is presented. Synthetic studies centred on three principal objectives. Firstly a series of structural analogues of MZP were prepared encompassing alkoxy, chloro and alkylamino substituents and evaluated, as the ethanesulphonate salts, for activity against mammalian DHFR. Inhibitory constant (KI) determinations were conducted by a Zone B analysis, the corresponding 4'-azido isomer of MZP proving more potent than the parent compound. Secondly, to facilitate metabolism and stability studies on MZP, a range of possible reference compounds were synthesised and characterised. Finally, a series of diaminopyrimidine derivatives were synthesised embracing structural features incompatible with DHFR inhibitory activity, in order that such compounds may serve as biochemical probes for the unidentified folate-independent target for lipophilic diaminopyrimidines discussed previously. Inactivity against DHFR was achieved via introduction of an ionic or basic group into a normally hydrophobic region of the molecule and compounds were screened against a mammalian DHFR and thymidylate synthase to confirm the abolition of activity. Several derivatives surprisingly proved potent inhibitors of DHFR exhibiting KI values comparable to that of methotrexate. Analogues were screened for antitumour activity in vitro and in vivo against murine leukaemia cell lines in order to identify potential lead compounds. Several derivatives virtually inactive against DHFR exhibited a disparate cytotoxicity and further biochemical studies are warranted. The nobreak hitherto unreported debenzylation of 2,4-diamino-5-(N-alkyl-benzylaminophenyl) pyrimidines was discovered during the course of the synthetic studies, treatment of these compounds with nitrous acid affording the corresponding benzotriazoles.

Oxidized phospholipid inhibition of toll-like receptor (TLR) signaling is restricted to TLR2 and TLR4 roles for cd14, lps-binding protein, and md2 as targets for specificity of inhibition

The generation of reactive oxygen species is a central feature of inflammation that results in the oxidation of host phospholipids. Oxidized phospholipids, such as 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC), have been shown to inhibit signaling induced by bacterial lipopeptide or lipopolysac-charide (LPS), yet the mechanisms responsible for the inhibition of Toll-like receptor (TLR) signaling by OxPAPC remain incompletely understood. Here, we examined the mechanisms by which OxPAPC inhibits TLR signaling induced by diverse ligands in macrophages, smooth muscle cells, and epithelial cells. OxPAPC inhibited tumor necrosis factor- production, IB degradation, p38 MAPK phosphorylation, and NF-B-dependent reporter activation induced by stimulants of TLR2 and TLR4 (Pam3CSK4 and LPS) but not by stimulants of other TLRs (poly(I·C), flagellin, loxoribine, single-stranded RNA, or CpG DNA) in macrophages and HEK-293 cells transfected with respective TLRs and significantly reduced inflammatory responses in mice injected subcutaneously or intraperitoneally with Pam3CSK4. Serum proteins, including CD14 and LPS-binding protein, were identified as key targets for the specificity of TLR inhibition as supplementation with excess serum or recombinant CD14 or LBP reversed TLR2 inhibition by OxPAPC, whereas serum accessory proteins or expression of membrane CD14 potentiated signaling via TLR2 and TLR4 but not other TLRs. Binding experiments and functional assays identified MD2 as a novel additional target of OxPAPC inhibition of LPS signaling. Synthetic phospholipid oxidation products 1-palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine inhibited TLR2 signaling from 30 µM. Taken together, these results suggest that oxidized phospholipid-mediated inhibition of TLR signaling occurs mainly by competitive interaction with accessory proteins that interact directly with bacterial lipids to promote signaling via TLR2 or TLR4.

Multiple roles of charged amino acids in cytoplasmic loop 7 for expression and function of the multidrug and organic anion transporter MRP1 (ABCC1)

Multidrug resistance protein MRP1 mediates the ATP-dependent efflux of many chemotherapeutic agents and organic anions. MRP1 has two nucleotide binding sites (NBSs) and three membrane spanning domains (MSDs) containing 17 transmembrane helices linked by extracellular and cytoplasmic loops (CL). Homology models suggest that CL7 (amino acids 1141-1195) is in a position where it could participate in signaling between the MSDs and NBSs during the transport process. We have individually replaced eight charged residues in CL7 with Ala, and in some cases, an amino acid with the same charge, and then investigated the effects on MRP1 expression, transport activity, and nucleotide and substrate interactions. A triple mutant in which Glu(1169), Glu(1170), and Glu(1172) were all replaced with Ala was also examined. The properties of R1173A and E1184A were comparable with those of wild-type MRP1, whereas the remaining mutants were either poorly expressed (R1166A, D1183A) or exhibited reduced transport of one or more organic anions (E1144A, D1179A, K1181A, (1169)AAQA). Same charge mutant D1183E was also not expressed, whereas expression and activity of R1166K were similar to wild-type MRP1. The moderate substrate-selective changes in transport activity displayed by mutants E1144A, D1179A, K1181A, and (1169)AAQA were accompanied by changes in orthovanadate-induced trapping of [alpha-(32)P]azidoADP by NBS2 indicating changes in ATP hydrolysis or release of ADP. In the case of E1144A, estradiol glucuronide no longer inhibited trapping of azidoADP. Together, our results demonstrate the extreme sensitivity of CL7 to mutation, consistent with its critical and complex dual role in both the proper folding and transport activity of MRP1.

Overcoming network overload and redundancy in inter-organizational networks:the roles of potential and latent ties

This paper builds on Granovetter's distinction between strong and weak ties [Granovetter, M. S. 1973. The strength of weak ties. Amer. J. Sociol. 78(6) 1360–1380] in order to respond to recent calls for a more dynamic and processual understanding of networks. The concepts of potential and latent tie are deductively identified, and their implications for understanding how and why networks emerge, evolve, and change are explored. A longitudinal empirical study conducted with companies operating in the European motorsport industry reveals that firms take strategic actions to search for potential ties and reactivate latent ties in order to solve problems of network redundancy and overload. Examples are given, and their characteristics are examined to provide theoretical elaboration of the relationship between the types of tie and network evolution. These conceptual and empirical insights move understanding of the managerial challenge of building effective networks beyond static structural contingency models of optimal network forms to highlight the processes and capabilities of dynamic relationship building and network development. In so doing, this paper highlights the interrelationship between search and redundancy and the scope for strategic action alongside path dependence and structural influences on network processes.

Mind-Reading Accuracy in Intimate Relationships:Assessing the Roles of the Relationship, the Target, and the Judge

Using a video-review procedure, multiple perceivers carried out mind-reading tasks of multiple targets at different levels of acquaintanceship (50 dating couples, friends of the dating partners, and strangers). As predicted, the authors found that mind-reading accuracy was (a) higher as a function of increased acquaintanceship, (b) relatively unaffected by target effects, (c) influenced by individual differences in perceivers' ability, and (d) higher for female than male perceivers. In addition, superior mind-reading accuracy (for dating couples and friends) was related to higher relationship satisfaction, closeness, and more prior disclosure about the problems discussed, but only under moderating conditions related to sex and relationship length. The authors conclude that the nature of the relationship between the perceiver and the target occupies a pivotal role in determining mind-reading accuracy.

Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species

Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H) with and without reoxygenation (H/R) in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS), we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2 -• scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2 -.To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4h hypoxia with and without 2h of reoxygenation and although cellular glutathione (GSH) was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage. © 2013 The Authors.

Structure-activity relationships of the N-terminus of calcitonin gene-related peptide:key roles of alanine-5 and threonine-6 in receptor activation

Background and purpose - The N-terminus of calcitonin gene-related peptide (CGRP) is important for receptor activation, especially the disulphide-bonded ring (residues 1-7). However, the roles of individual amino acids within this region have not been examined and so the molecular determinants of agonism are unknown. This study has examined the role of residues 1, 3-6 and 8-9, excluding Cys-2 and Cys-7. Experimental approach - CGRP derivatives were substituted with either cysteine or alanine; further residues were introduced at position 6. Their affinity was measured by radioligand binding and their efficacy by measuring cAMP production in SK-N-MC cells and ß-arrestin 2 translocation in CHO-K1 cells at the CGRP receptor. Key results - Substitution of Ala-5 by cysteine reduced affinity 270-fold and reduced efficacy for production of cAMP in SK-N-MCs. Potency at ß-arrestin translocation was reduced by 9-fold. Substitution of Thr-6 by cysteine destroyed all measurable efficacy of both cAMP and ß-arrestin responses; substitution with either alanine or serine impaired potency. Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10-fold reductions in potency at both responses. Similar observations were made at a second CGRP-activated receptor, the AMY1(a) receptor. Conclusions and implications - Ala-5 and Thr-6 are key determinants of agonist activity for CGRP. Ala-5 is also very important for receptor binding. Residues outside of the 1-7 ring also contribute to agonist activity.