Spirituality at work: The development of a theoretical model

Spirituality at work has received much interest in recent years, and a stream of research notes its benefits beyond a trend. Despite the topic’s growing recognition, the research community raised the need for the integration of spirituality at work with traditional areas of investigation (Giacalone & Jurkiewicz, 2003). A potentially fruitful first step towards this involves use of person-organisation (PO) fit theory (Ashforth & Pratt, 2003; Sheep, 2004, 2006; Singhal & Chatterjee, 2006; Singhal, 2007). The purpose of this study is to build upon initial attempts towards this integration and to promote further acknowledgement of the potential benefits of incorporating spirituality at work into wider organisational psychology frameworks. This was achieved by integrating both PO fit and transpersonal psychology, and subsequently developing a theoretical model that investigates three questions: a) what antecedents lead individuals and organisations to seek spirituality at work?, b) what are the perceived spiritual preferences (needs) of individuals and how are those preferences fulfilled through the context of the workplace (supplies)?, and c) what are the consequences of meeting spiritual preferences (needs), as perceived by individuals? Using constructivist grounded theory, analysis of interview data from thirty-four participants located in organisations (one spiritual and three non-spiritual) across The Netherlands, Ireland, the United Kingdom and Portugal led to a theory in which I propose a core category of reconciling self as a critical factor of spirituality at work. Reconciling self captures the process whereby the self consistently attempts to maintain a congruent relationship with the ego and the environment, and this construct emerged as the primary concern for participants. Reconciling self was influenced largely by meaning and purpose and the need to connect to something larger than oneself, and through the organisation making a difference. The congruence or perceived fit within the workplace was captured through the action strategy conscious reconciling experiences; in the case where the immediacy of such expression was compromised, reconciling self was noted through the action strategy active adjustment. The action strategies were influenced through a set of intervening conditions that included a set of spirituality at work needs and supplies, through a context that emphasised attributes such as spiritual values, a culture that focused on openness and support, and relational leadership. The consequences of spirituality at work included benefits such as individual job satisfaction, positivity and self-realisation, and organisational outcomes as being a force for good and fostering employee commitment. The contribution of this study includes a new theoretical model concerning why, when, and how spirituality at work influences individual and organisational processes and outcomes. Such understanding contributes to better understanding of spirituality at work, and identifies ways in which PO fit occurs within a broader psychological context than that proposed in mainstream organisational psychology (i.e. through reconciling self influenced by meaning and purpose, the need to connect to something larger than oneself, and a set of spirituality at work needs). These findings reduce the PO fit gap. Implications of the study include the findings that spirituality at work creates positive outcomes, and insistence on the role of connecting to something larger than oneself implies individuals are always in the process of moving toward reconciling self. Organisations should consider their ability to harness latent human potential and transcendence by extending self-boundaries and developing the self. Limitations and future research directions are discussed

Radical approaches to alangium and mitragyna alkaloids

Abstract The work presented in this thesis has focused on the development of novel and concise syntheses of Alangium and Mitragyna alkaloids, and especial approaches towards (±)-protoemetinol (a), which is a key precursor of a range of Alangium alkaloids such as psychotrine (b) and deoxytubulosine (c). The approaches include the use of a key radical cyclisation to form the tri-cyclic core. Chapter 1 gives a general overview of radical chemistry and it focuses on the application of radical intermolecular and intramolecular reactions in synthesis. Consideration is given to the mediator of radical reactions from the classic organotin reagents, to more recently developed alternative hydrides. An overview of previous synthetic approaches to a range of Alangium and Mitragyna alkaloids is then explored. Chapter 2 follows on from previous work within our group, involving the use of phosphorus hydride radical addition reactions, to alkenes or dienes, followed by a subsequent Horner-Wadsworth-Emmons reaction. It was expected that the tri-cyclic core of the Alangium alkaloids could be prepared by cyclisation of a 1,7-diene, using a phosphorus hydride to afford the phosphonate or phosphonothioate, however this approach was unsuccessful and it highlighted some limitations of the methodology. Chapter 3 explores the radical and ionic chemistry of a range of silanes. Initial studies explored the radical addition of a range of silicon hydrides to alkenes to afford the corresponding hydrosilylation products. The chemistry of the hydrosilylation products was then explored – it was hoped that a subsequent Peterson olefination or Fleming-Tamao oxidation would afford the corresponding alkene or alcohol. Subsequent investigations looked into the possibility of combining the radical and ionic reactions, to afford alkenes or alcohols, in a one-pot transformation. Chapter 4 explores the radical cyclisation of various compounds, including unsaturated alpha-haloamides (d and e), xanthates (f), vinyl bromides (g and h). For this, a robust and efficient synthesis of an allyl tetrahydroisoquinoline core (i and j) was developed, following conversion into the desired radical precursors these compounds were treated with tributyltin hydride and a radical initiator. Finally, Chapter 4 investigates the radical cyclisation of some unsaturated phenylselenides (k and l), which resulted in the isolation of the desired target alkaloid (±)-protoemetinol (a) in 4 steps and in 2% overall yield. Chapter 5, which builds on previous work within Chapter 4, discusses the cyclisation of vinyl bromides bearing an a,β-unsaturated ester (n and o). This resulted in short 4-step syntheses of both (±)-des-methyl-protoemetinol (m) and (±)-protoemetinol (a) (along with some epimers). Subsequent studies then expanded the synthetic strategy to include the synthesis of a structurally simpler analogue of mitragynine (p).EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The impact of macrocycle conformation on the taxadiene-forming carbocation cascade: insight gained from sobralene, a recently discovered verticillene isomer

This is an accepted manuscript of an article published by American Chemical Society in Journal of Organic Chemistry on 26/02/2020, available online: https://doi.org/10.1021/acs.joc.0c00369 The accepted version of the publication may differ from the final published version.Copyright © 2020 American Chemical Society. DFT calculations on the carbocation intermediates that connect the biosynthetic pathways leading to the sand fly pheromone sobralene and taxadiene have been made. Establishment of the conformation of the macrocyclic carbocation intermediate required to produce the (Z)-C8,C9 alkene bond in sobralene has identified new conformations of the verticillyl carbocation intermediates on the taxadiene biosynthetic pathway. These "sobralene-like" carbocation conformations provide an exothermic pathway to taxadiene and are validated by comparison to closely related structures (X-ray and NMR).The University of NottinghamPublished versio

Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase

Mobilization of bone marrow eosinophils is a critical early step in their trafficking to the lung during allergic inflammatory reactions. We have shown previously that the cytokine interleukin (IL)-5, generated during an allergic inflammatory reaction in the guinea pig, acts systemically to mobilize eosinophils from the bone marrow. Here, we have investigated the mechanisms underlying this release process. Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5. Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow. Eosinophils released from the bone marrow in response to IL-5 expressed increased levels of β2 integrin and a decrease in L-selectin, but no change in α4 integrin levels. A β2 integrin–blocking antibody markedly inhibited the mobilization of eosinophils from the bone marrow stimulated by IL-5. In contrast, an α4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5. In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system. The parallel observations on the bone marrow eosinophil release process and responses in isolated eosinophils in vitro suggest that eosinophil chemokinesis is the driving force for release in vivo and that this release process is regulated by α4 and β2 integrins acting in opposite directions

Certolizumab pegol in the treatment of rheumatoid arthritis: a comprehensive review of its clinical efficacy and safety

Biological agents, including TNF inhibitors, have revolutionized the treatment of RA in recent years. Certolizumab pegol (CZP) is a novel pegylated anti-TNF approved for the treatment of adult patients with moderately to severely active RA. This article provides an overview of three published clinical trials of CZP in RA in patients with active disease who have shown an inadequate response to DMARDs, including MTX: RA prevention of structural damage (RAPID) 1 and 2, which evaluated the efficacy and safety of CZP added to MTX when dosed every 2 weeks, and efficacy and safety of CZP – 4 weekly dosage in rheumatoid arthritis (FAST4WARD), which evaluated CZP monotherapy when dosed every 4 weeks. In the trials, CZP plus MTX or as monotherapy significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage as early as Week 16 of the treatment. In addition, CZP treatment significantly improved patient-reported outcome measures, providing significant reductions in pain and fatigue and improvements in physical function as early as Week 1 of treatment; improvements in health-related quality of life were evident at the first assessment at Week 12. CZP treatment improved productivity at work, significantly reducing the number of days of missed work as well as the number of days with reduced productivity, and also increased productivity within the home and improved participation in family, social and leisure activities. CZP was generally well tolerated when used either as monotherapy or added to MTX; most adverse events were mild or moderate. Taken together, the results of these trials suggest that CZP is an effective new option for the treatment of RA

Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. The natural product (+)-grandifloracin is a potent “anti-austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti-austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthesis and biological evaluation of racemic analogues of grandifloracin bearing diverse sidechains, of which two show enhanced potency in comparison with the natural product. Additionally, several unexpected by-products containing modifications of the grandifloracin core were isolated, identified and similarly evaluated for biological activity.We thank EPSRC (DTP studentship to B.E.A.) and Cancer Research at Bath (CR@B) for funding. The biological investigation was supported by a grant from the Japanese Society for the Promotion of Science (JSPS Kakenhi #16 K08319) and the Kobayashi International Scholarship Foundation to S.A.Published versio

A Novel Endothelial L-Selectin Ligand Activity in Lymph Node Medulla That Is Regulated by α(1,3)-Fucosyltransferase-IV

Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules (HEVs) in the subcortex and incrementally larger collecting venules in the medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling. L-selectin counterreceptors in HEVs are recognized by mAb MECA-79, a surrogate marker for molecularly heterogeneous glycans termed peripheral node addressin. By contrast, we find that medullary venules express L-selectin ligands not recognized by MECA-79. Both L-selectin ligands must be fucosylated by α(1,3)-fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII−/− mice. Intravital microscopy experiments revealed that MECA-79–reactive ligands depend primarily on FucT-VII, whereas MECA-79–independent medullary L-selectin ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled these anatomical distinctions. The relative mRNA level of FucT-IV was higher in medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally confined to contiguous microvascular domains in PLNs. Although MECA-79–reactive species predominate in HEVs, medullary venules express another ligand that is spatially, antigenically, and biosynthetically unique. Physiologic relevance for this novel activity in medullary microvessels is suggested by the finding that L-selectin–dependent T cell homing to PLNs was partly insensitive to MECA-79 inhibition

Synthesis of triazole-linked morpholino oligonucleotides via Cu1 catalysed cycloaddition

Triazole-linked morpholino (TLMO) oligonucleic acids were synthesised using the CuI catalysed (3 + 2) azide–alkyne cycloaddition (CuAAC) reaction. The modified DNA analogues were incorporated into 13-mer sequences via solid phase synthesis. UV melting experiments showed that the TLMO modification gives higher Tm values than the corresponding TLDNA modification