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1. Chapter 5 Women and Minority Expatriates

Author

Shortland, Susan and Perkins, Stephen J.

Subjects
expatriate experience, diversity, diversity training, bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJM Management & management techniques::KJMV Management of specific areas::KJMV2 Personnel & human resources management, bic Book Industry Communication::K Economics, finance, business & management::KJ Business & management::KJU Organizational theory & behaviour, bic Book Industry Communication::J Society & social sciences::JM Psychology, bic Book Industry Communication::J Society & social sciences::JM Psychology::JMJ Occupational & industrial psychology
Abstract

There has been several decades of research on why women are under-represented in the expatriate population, but it is only in the past few years that research has begun to focus on issues with members from other diverse groups and how they fit into the expatriate picture. This chapter’s authors spotlight gender, age, race, religion and sexual orientation diversity. They point out, however, that MNCs can help alleviate some of these issues by fostering strong diversity climates within the firm, including diversity training programs, but clear evidence for the success of the various attempts to increase diversity is lacking. This chapter highlights how there is a special need for research which considers the intersection of these various dimensions of diversity, and how that can affect expatriate experience.

Published
2023
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2. Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix Jo-Bamba, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H. Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J., Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice Ann, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P., Gallagher, Hugh, Game, David, Garcia, Eva Lozano, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P.J., Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A., Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Frankl, Fiona Karet, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P., Maggie Lai, Ling Wai, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J., Mark, Patrick B., Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM., Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J., Persu, Alexandre, Petchey, William G., Pickering, Matthew C., Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian SD., Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, R.N., Sandu, Kanwaljit S., Sarween, Nadia, Sayer, John A., Sebire, Neil, Selvaskandan, Haresh, Shah, Sapna, Sharma, Asheesh, Sharples, Edward J., Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A. Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B., Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin Iain, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H., Wilson, Patricia D., Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Griffin, Sian, Hall, Matt, Karet Frankl, Fiona, Maher, Eamonn R., Pinney, Jenny, Tam, Frederick W.K., Wilson, Patricia, Sy, Karla Therese L., Huang, Kui, Ye, Jamie, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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4. Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Author

Abat, Sharirose, Adalat, Shazia, Agbonmwandolor, Joy, Ahmad, Zubaidah, Alejmi, Abdulfattah, Almasarwah, Rashid, Annear, Nicholas, Asgari, Ellie, Ayers, Amanda, Baharani, Jyoti, Balasubramaniam, Gowrie, Kpodo, Felix, Bansal, Tarun, Barratt, Alison, Barratt, Jonathan, Bates, Megan, Bayne, Natalie, Bendle, Janet, Benyon, Sarah, Bergmann, Carsten, Bhandari, Sunil, Bingham, Coralie, Boddana, Preetham, Bond, Sally, Braddon, Fiona, Bramham, Kate, Branson, Angela, Brearey, Stephen, Brocklebank, Vicky, Budwal, Sharanjit, Byrne, Conor, Cairns, Hugh, Camilleri, Brian, Campbell, Gary, Capell, Alys, Carmody, Margaret, Carson, Marion, Cathcart, Tracy, Catley, Christine, Cesar, Karine, Chan, Melanie, Chea, Houda, Chess, James, Cheung, Chee Kay, Chick, Katy-Jane, Chitalia, Nihil, Christian, Martin, Chrysochou, Tina, Clark, Katherine, Clayton, Christopher, Clissold, Rhian, Cockerill, Helen, Coelho, Joshua, Colby, Elizabeth, Colclough, Viv, Conway, Eileen, Cook, H Terence, Cook, Wendy, Cooper, Theresa, Coward, Richard J, Crosbie, Sarah, Cserep, Gabor, Date, Anjali, Davidson, Katherine, Davies, Amanda, Dhaun, Neeraj, Dhaygude, Ajay, Diskin, Lynn, Dixit, Abhijit, Doctolero, Eunice, Dorey, Suzannah, Downard, Lewis, Drayson, Mark, Dreyer, Gavin, Dutt, Tina, Etuk, Kufreabasi, Evans, Dawn, Finch, Jenny, Flinter, Frances, Fotheringham, James, Francis, Lucy, Gale, Daniel P, Gallagher, Hugh, Game, David, Garcia, Eva, Gavrila, Madita, Gear, Susie, Geddes, Colin, Gilchrist, Mark, Gittus, Matt, Goggolidou, Paraskevi, Goldsmith, Christopher, Gooden, Patricia, Goodlife, Andrea, Goodwin, Priyanka, Grammatikopoulos, Tassos, Gray, Barry, Griffith, Megan, Gumus, Steph, Gupta, Sanjana, Hamilton, Patrick, Harper, Lorraine, Harris, Tess, Haskell, Louise, Hayward, Samantha, Hegde, Shivaram, Hendry, Bruce, Hewins, Sue, Hewitson, Nicola, Hillman, Kate, Hiremath, Mrityunjay, Howson, Alexandra, Htet, Zay, Huish, Sharon, Hull, Richard, Humphries, Alister, Hunt, David P J, Hunter, Karl, Hunter, Samantha, Ijeomah-Orji, Marilyn, Inston, Nick, Jayne, David, Jenfa, Gbemisola, Jenkins, Alison, Johnson, Sally, Jones, Caroline A, Jones, Colin, Jones, Amanda, Jones, Rachel, Kamesh, Lavanya, Kanigicherla, Durga, Karet Frankl, Fiona, Karim, Mahzuz, Kaur, Amrit, Kavanagh, David, Kearley, Kelly, Kerecuk, Larissa, Khwaja, Arif, King, Garry, King, Grant, Kislowska, Ewa, Klata, Edyta, Kokocinska, Maria, Lambie, Mark, Lawless, Laura, Ledson, Thomas, Lennon, Rachel, Levine, Adam P, Lai, Ling Wai Maggie, Lipkin, Graham, Lovitt, Graham, Lyons, Paul, Mabillard, Holly, Mackintosh, Katherine, Mahdi, Khalid, Maher, Eamonn, Marchbank, Kevin J, Mark, Patrick B, Masoud, Sherry, Masunda, Bridgett, Mavani, Zainab, Mayfair, Jake, McAdoo, Stephen, Mckinnell, Joanna, Melhem, Nabil, Meyrick, Simon, Moochhala, Shabbir, Morgan, Putnam, Morgan, Ann, Muhammad, Fawad, Murray, Shona, Novobritskaya, Kristina, Ong, Albert CM, Oni, Louise, Osmaston, Kate, Padmanabhan, Neal, Parkes, Sharon, Patrick, Jean, Pattison, James, Paul, Riny, Percival, Rachel, Perkins, Stephen J, Persu, Alexandre, Petchey, William G, Pickering, Matthew C, Pinney, Jennifer, Pitcher, David, Plumb, Lucy, Plummer, Zoe, Popoola, Joyce, Post, Frank, Power, Albert, Pratt, Guy, Pusey, Charles, Rabara, Ria, Rabuya, May, Raju, Tina, Javier, Chadd, Roberts, Ian S D, Roufosse, Candice, Rumjon, Adam, Salama, Alan, Saleem, Moin, Sandford, Richard, Sandu, Kanwaljit S, Sarween, Nadia, Sayer, John A, Sebire, Neil, Selvaskandan, Haresh, Sharma, Asheesh, Sharples, Edward J, Sheerin, Neil, Shetty, Harish, Shroff, Rukshana, Simms, Roslyn, Sinha, Manish, Sinha, Smeeta, Smith, Kerry, Smith, Lara, Srivastava, Shalabh, Steenkamp, Retha, Stott, Ian, Stroud, Katerina, Swift, Pauline, Szklarzewicz, Justyna, Tam, Fred, Tan, Kay, Taylor, Robert, Tischkowitz, Marc, Thomas, Kay, Tse, Yincent, Turnbull, Alison, Turner, A Neil, Tyerman, Kay, Usher, Miranda, Venkat-Raman, Gopalakrishnan, Walker, Alycon, Walsh, Stephen B, Waters, Aoife, Watt, Angela, Webster, Phil, Wechalekar, Ashutosh, Welsh, Gavin I, West, Nicol, Wheeler, David, Wiles, Kate, Willcocks, Lisa, Williams, Angharad, Williams, Emma, Williams, Karen, Wilson, Deborah H, Wilson, Patricia D, Winyard, Paul, Wong, Edwin, Wong, Katie, Wood, Grahame, Woodward, Emma, Woodward, Len, Woolf, Adrian, Wright, David, Downward, Lewis, Chrysochou, Constantina, Griffin, Sian, Hall, Matt, Maher, Eamonn R, Pinney, Jenny, Tam, Frederick W K, Turner, Andrew Neil, Wilson, Patricia, Taylor, Christopher Mark, Nitsch, Dorothea, and Bockenhauer, Detlef

Published
2024
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13. Using atomistic solution scattering modelling to elucidate the role of the Fc glycans in human IgG4.

Author

Spiteri, Valentina A., Doutch, James, Rambo, Robert P., Bhatt, Jayesh S., Gor, Jayesh, Dalby, Paul A., and Perkins, Stephen J.

Subjects
GLYCANS, MONTE Carlo method, NEUTRON scattering, SMALL-angle neutron scattering, PRINCIPAL components analysis, X-ray scattering, IMMUNOGLOBULIN G
Abstract

Human immunoglobulin G (IgG) exists as four subclasses IgG1-4, each of which has two Fab subunits joined by two hinges to a Fc subunit. IgG4 has the shortest hinge with 12 residues. The Fc subunit has two glycan chains, but the importance of glycosylation is not fully understood in IgG4. Here, to evaluate the stability and structure of non-glycosylated IgG4, we performed a multidisciplinary structural study of glycosylated and deglycosylated human IgG4 A33 for comparison with our similar study of human IgG1 A33. After deglycosylation, IgG4 was found to be monomeric by analytical ultracentrifugation; its sedimentation coefficient of 6.52 S was reduced by 0.27 S in reflection of its lower mass. X-ray and neutron solution scattering showed that the overall Guinier radius of gyration RG and its cross-sectional values after deglycosylation were almost unchanged. In the P(r) distance distribution curves, the two M1 and M2 peaks that monitor the two most common distances within IgG4 were unchanged following deglycosylation. Further insight from Monte Carlo simulations for glycosylated and deglycosylated IgG4 came from 111,382 and 117,135 possible structures respectively. Their comparison to the X-ray and neutron scattering curves identified several hundred best-fit models for both forms of IgG4. Principal component analyses showed that glycosylated and deglycosylated IgG4 exhibited different conformations from each other. Within the constraint of unchanged RG and M1-M2 values, the glycosylated IgG4 models showed more restricted Fc conformations compared to deglycosylated IgG4, but no other changes. Kratky plots supported this interpretation of greater disorder upon deglycosylation, also observed in IgG1. Overall, these more variable Fc conformations may demonstrate a generalisable impact of deglycosylation on Fc structures, but with no large conformational changes in IgG4 unlike those seen in IgG1. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Quantum accountability: when does enough become too much in top pay decision-making?

Author

Shortland, Susan and Perkins, Stephen J.

Subjects
WAGES, DECISION making, INSTITUTIONAL investors, EXECUTIVE compensation
Abstract

Purpose: The purpose of this paper is to examine how and why individuals involved in executive remuneration (top pay) decision-making consider quantum as being appropriate rather than excessive, theorised under the rubric of accountability. Design/methodology/approach: In-depth interviews were conducted with non-executive directors (NEDs) serving on remuneration committees (Remcos), institutional investors, their external advisers and internal HR reward experts. Transcripts were analysed using NVivo and the Gioia qualitative methodology. Findings: Defining, measuring and applying performance conditionality in the determination of top pay quantum such that it aligns with company strategy/culture and values, as well as individual recipient motivations, is difficult. While creative approaches to setting top pay so as to attract, retain and motivate key personnel are welcomed, these risk Remco members' personal/organisational reputations. Members recognise disconnection between top pay quantum and general pay levels and how the media highlights social inequality leading to public distrust. They believe they can contribute to more socially acceptable quantum by applying their own values in top pay decision-making. Originality/value: Sanctions-based, trust-based and selection/peer networks/felt-based accountability theory is used to explain decision-makers' actions when determining top pay quantum. This paper extends felt accountability theory to encompass public/societal accountability in the context of the appropriateness of top pay quantum decisions. [ABSTRACT FROM AUTHOR]

Published
2023
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21. The solution structure of the unbound IgG Fc receptor CD64 resembles its crystal structure: Implications for function.

Author

Hui, Gar Kay, Gao, Xin, Gor, Jayesh, Lu, Jinghua, Sun, Peter D., and Perkins, Stephen J.

Subjects
FC receptors, CRYSTAL structure, IMMUNE complexes, SMALL-angle X-ray scattering, DENDRITIC cells, IMMUNOGLOBULINS, IMMUNE response, IMMUNOGLOBULIN G
Abstract

FcγRI (CD64) is the only high-affinity Fcγ receptor found on monocytes, macrophages, eosinophils, neutrophils and dendritic cells. It binds immunoglobulin G (IgG) antibody-antigen complexes at its Fc region to trigger key immune responses. CD64 contains three immunoglobulin-fold extracellular domains (D1, D2 and D3) and a membrane-spanning region. Despite the importance of CD64, no solution structure for this is known to date. To investigate this, we used analytical ultracentrifugation, small-angle X-ray scattering, and atomistic modelling. Analytical ultracentrifugation revealed that CD64 was monomeric with a sedimentation coefficient s020,w of 2.53 S, together with some dimer. Small-angle X-ray scattering showed that its radius of gyration RG was 3.3–3.4 nm and increased at higher concentrations to indicate low dimerization. Monte Carlo modelling implemented in the SASSIE-web package generated 279,162 physically-realistic trial CD64 structures. From these, the scattering best-fit models at the lowest measured concentrations that minimised dimers revealed that the D1, D2 and D3 domains were structurally similar to those seen in three CD64 crystal structures, but showed previously unreported flexibility between D1, D2 and D3. Despite the limitations of the scattering data, the superimposition of the CD64 solution structures onto crystal structures of the IgG Fc-CD64 complex showed that the CD64 domains do not sterically clash with the IgG Fc region, i.e. the solution structure of CD64 was sufficiently compact to allow IgG to bind to its high-affinity Fcγ receptor. This improved understanding may result in novel approaches to inhibit CD64 function, and opens the way for the solution study of the full-length CD64-IgG complex. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Identification of diverse lipid‐binding modes in the groove of zinc α2 glycoprotein reveals its functional versatility

Author

Zahid, Henna, Lau, Andy M., Kelly, Sharon M., Karu, Kersti, Gor, Jayesh, Perkins, Stephen J., and McDermott, Lindsay C.

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16-BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16-BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related Cluster of differentiation 1 proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16-BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16-BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16-BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16-BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16-BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand.

Published
2022

23. Pluralistic Tensions in Expatriating Managers

Author

Perkins, Stephen J. and Daste, Romain

Abstract

Purpose--The purpose of this article is to enhance understanding of influences on interaction between corporate personnel and development specialists and line functions associated with expatriating managers. Line managers are expected to accept greater responsibility for people management and development. But line managers' strategies for managing risks inherent in supervising expatriate managers may cause to surface incompatibilities with specialists' corporate "policy conscience" role. A pluralistically inclined perspective on "managerial interest streams" offers insights into inter-group perceptions and behaviour. Design/methodology/approach--Focusing on organisational actors' interpretations, a non-standardised survey by e-mail, covering a small sample of expatriate managers (n=20) employed in various countries by a large UK-headquartered healthcare retail group, was complemented by semi-structured interviews with personnel and development specialists in a further seven large multinational companies. Findings--Potential tensions around the application of corporate expatriation policy may be attributed to factors "educating" line and specialist orientations to expatriate managers. Originality/value--The value of the paper is in the development of an original model sketching pluralistically located interaction around expatriation management. While limited to an exploratory empirical investigation, the practical implications derive from specification of opportunities and threats to partnership building between those involved in expatriating managers. (Contains 1 figure.)

Published
2007
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32. Identification of diverse lipid‐binding modes in the groove of zinc α2 glycoprotein reveals its functional versatility.

Author

Zahid, Henna, Lau, Andy M., Kelly, Sharon M., Karu, Kersti, Gor, Jayesh, Perkins, Stephen J., and McDermott, Lindsay C.

Subjects
ZINC, MOLECULAR docking, BINDING sites, PROTEIN folding, FATTY acids, ZINC-finger proteins
Abstract

ZAG is a multifunctional glycoprotein with a class I MHC‐like protein fold and an α1‐α2 lipid‐binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16‐BODIPY. Here, the molecular basis for this difference was elucidated. Multi‐wavelength analytical ultracentrifugation confirmed that DAUDA and C16‐BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid‐binding in the structurally related Cluster of differentiation 1 proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16‐BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16‐BODIPY but not of DAUDA compared to wild‐type ZAG and showed that C16‐BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16‐BODIPY. We conclude that the ZAG α1‐α2 groove contains separate but overlapping sites for DAUDA and C16‐BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand. [ABSTRACT FROM AUTHOR]

Published
2022
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33. The EAHAD Coagulation Factor Variant Databases: important resources for haemostasis clinicians and researchers

Author

McVey, John, Rallapalli, Pavithra M., Kemball-Cook, Geoffrey, Hampshire, Daniel J., Giansily-Blaizot, Muriel, Gomez, Keith, Perkins, Stephen J., and Ludlam, Christopher A.

Abstract

Introduction: Advances in genomic sequencing have facilitated the sequencing of genes associated with disorders of haemostasis. The identification of variants within genes, access to curated data incorporating structural, functional, evolutionary as well as phenotypic data has become increasingly important in order to ascribe pathogenicity. Aim: The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factor Variant Database Project aims to provide a single port of entry to a web accessible resource for variants in genes involved in clinical bleeding disorders. Results: New databases have evolved from previously developed single gene variant coagulation database projects, incorporating new data, new analysis tools and a new common database architecture with new interfaces and filters. These new databases currently present information about the genotype, phenotype (laboratory and clinical) and structural and functional effects of variants described in the genes of factor (F) VII (F7), FVIII (F8), FIX (F9) and von Willebrand factor (VWF). Conclusion: The project has improved the quality and quantity of information available to the haemostasis research and clinical communities, thereby enabling accurate classification of disease severity in order to make assessments of likely pathogenicity.

Published
2020

34. The Oxford Handbook of Organizational Theory: Meta-Theoretical Perspectives

Author

Olson, Naomi, Perkins, Stephen J., Mantere, Saku, Usdiken, Behlul, and Wexler, Mark

Subjects
The Oxford Handbook of Organizational Theory: Meta-Theoretical Perspectives (Book) -- Book reviews, The Blackwell Companion to Organizations (Book), Books -- Book reviews, Business, Business, general
Published
2004

37. Non-linearity of the collagen triple helix in solution and implications for collagen function

Author

Walker, Kenneth T., Nan, Ruodan, Wright, David W., Gor, Jayesh, Bishop, Anthony C., Makhatadze, George I., Brodsky, Barbara, and Perkins, Stephen J.

Subjects
collagen, Models, Molecular, Protein Conformation, Crystallography, X-Ray, molecular dynamics, Peptide Fragments, small-angle scattering, ultracentrifugation, atomistic modelling, Humans, Research Articles, Research Article
Abstract

Collagen adopts a characteristic supercoiled triple helical conformation which requires a repeating (Xaa-Yaa-Gly)n sequence. Despite the abundance of collagen, a combined experimental and atomistic modelling approach has not so far quantitated the degree of flexibility seen experimentally in the solution structures of collagen triple helices. To address this question, we report an experimental study on the flexibility of varying lengths of collagen triple helical peptides, composed of six, eight, ten and twelve repeats of the most stable Pro-Hyp-Gly (POG) units. In addition, one unblocked peptide, (POG)10unblocked, was compared with the blocked (POG)10 as a control for the significance of end effects. Complementary analytical ultracentrifugation and synchrotron small angle X-ray scattering data showed that the conformations of the longer triple helical peptides were not well explained by a linear structure derived from crystallography. To interpret these data, molecular dynamics simulations were used to generate 50 000 physically realistic collagen structures for each of the helices. These structures were fitted against their respective scattering data to reveal the best fitting structures from this large ensemble of possible helix structures. This curve fitting confirmed a small degree of non-linearity to exist in these best fit triple helices, with the degree of bending approximated as 4–17° from linearity. Our results open the way for further studies of other collagen triple helices with different sequences and stabilities in order to clarify the role of molecular rigidity and flexibility in collagen extracellular and immune function and disease.

Published
2017

40. Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS)1

Author

Perkins, Stephen J., Wright, David W., Zhang, Hailiang, Brookes, Emre H., Chen, Jianhan, Irving, Thomas C., Krueger, Susan, Barlow, David J., Edler, Karen J., Scott, David J., Terrill, Nicholas J., King, Stephen M., Butler, Paul D., and Curtis, Joseph E.

Subjects
Astrophysics::High Energy Astrophysical Phenomena, small-angle-neutron scattering (SANS), molecular dynamics (MD), Research Papers, molecular modelling, scattering curve fits, small-angle-X-ray scattering (SAXS)
Abstract

The CCP-SAS project is currently developing software for the atomistic and coarse-grained molecular modelling of X-ray and neutron small-angle scattering data. Its computational framework is described, alongside applications in biology and soft matter., The capabilities of current computer simulations provide a unique opportunity to model small-angle scattering (SAS) data at the atomistic level, and to include other structural constraints ranging from molecular and atomistic energetics to crystallography, electron microscopy and NMR. This extends the capabilities of solution scattering and provides deeper insights into the physics and chemistry of the systems studied. Realizing this potential, however, requires integrating the experimental data with a new generation of modelling software. To achieve this, the CCP-SAS collaboration (http://www.ccpsas.org/) is developing open-source, high-throughput and user-friendly software for the atomistic and coarse-grained molecular modelling of scattering data. Robust state-of-the-art molecular simulation engines and molecular dynamics and Monte Carlo force fields provide constraints to the solution structure inferred from the small-angle scattering data, which incorporates the known physical chemistry of the system. The implementation of this software suite involves a tiered approach in which GenApp provides the deployment infrastructure for running applications on both standard and high-performance computing hardware, and SASSIE provides a workflow framework into which modules can be plugged to prepare structures, carry out simulations, calculate theoretical scattering data and compare results with experimental data. GenApp produces the accessible web-based front end termed SASSIE-web, and GenApp and SASSIE also make community SAS codes available. Applications are illustrated by case studies: (i) inter-domain flexibility in two- to six-domain proteins as exemplified by HIV-1 Gag, MASP and ubiquitin; (ii) the hinge conformation in human IgG2 and IgA1 antibodies; (iii) the complex formed between a hexameric protein Hfq and mRNA; and (iv) synthetic ‘bottlebrush’ polymers.

Published
2016

42. The Interactive Factor H-Atypical Hemolytic Uremic Syndrome Mutation Database and Website: Update and Integration of Membrane Cofactor Protein and Factor I Mutations With Structural Models

Author

Saunders, Rebecca E., Abarrategui-Garrido, Cynthia, Frémeaux-Bacchi, Véronique, de Jorge, Elena Goicoechea, Goodship, Timothy H.J., Trascasa, Margarita López, Noris, Marina, Ponce Castro, Isabel Maria, Remuzzi, Giuseppe, de Córdoba, Santiago Rodríguez, Sánchez-Corral, Pilar, Skerka, Christine, Zipfel, Peter F., and Perkins, Stephen J.

Published
2007
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43. Segmenting international assignments: organizational justice

Author

Shortland, Susan, Perkins, Stephen J., and Perkins, Stephen

Subjects
Business-and-management, management
Abstract

This chapter begins by briefly examining the typical content of expatriate reward policy. Following on from this, it addresses the trend to segment international assignment policies to reflect different assignment types and provide flexibility to organisations, while simultaneously attempting to reduce costs and maximise expatriate return on investment. It then takes as its focus theoretical frameworks that can help expatriate reward professionals to predict outcomes of their policy design choices. In so doing, it first examines the role of equalising differences or compensating differentials theory (Rosen, 1986) as a basis to justify differential treatment in expatriate reward within a segmented international assignment policy suite. Next, it reviews the impact of equity (and perceived inequity) (Adams, 1963) within a segmented policy approach on assignees’ potential willingness to accept assignments and remain satisfied with - and motivated by - reward policy while on assignment. \ud Finally, the chapter draws upon the organisational justice literature to consider the reasonableness of procedures, the context surrounding these and the (unintended?) consequences of policy outcomes (Byrne and Cropanzano, 2001; Colquitt, Greenberg and Zapata-Phelan, 2005; Hansen, Byrne and Kiersch, 2013). ‘Distributive’ justice (Chory and Kingsley Westerman, 2009; Homans, 1961) is proposed as an appropriate theoretical framework to help predict assignees’ evaluation of what they receive compared to others; ‘procedural’ justice is set out as a frame to assist policy implementers to determine how outcomes are allocated (Palaiologos, Papazekos and Panayotopoulou, 2011); and ‘interactional’ justice is presented to address how decisions are communicated and implemented (Brown, Bemmels and Barclay, 2010; Gilliland, Gross and Hogler, 2014).

Published
2018

49. SCT: a suite of programs for comparing atomistic models with small-angle scattering data

Author

Wright, David W. and Perkins, Stephen J.

Subjects
hydration shells, constrained modelling, neutron scattering, X-ray scattering, analytical ultracentrifugation, Computer Programs
Abstract

The SCT suite of tools for the atomistic modelling of X-ray and neutron scattering curves has resulted in 77 macromolecular structures to date. SCT is now made publicly available as open source, alongside an easier-to-use reimplementation of the same algorithms in Python., Small-angle X-ray and neutron scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are of particular utility when large proteins cannot be crystallized or when the structure is altered by solution conditions. Atomistic models of the averaged structure can be generated through constrained modelling, a technique in which known domain or subunit structures are combined with linker models to produce candidate global conformations. By randomizing the configuration adopted by the different elements of the model, thousands of candidate structures are produced. Next, theoretical scattering curves are generated for each model for trial-and-error fits to the experimental data. From these, a small family of best-fit models is identified. In order to facilitate both the computation of theoretical scattering curves from atomistic models and their comparison with experiment, the SCT suite of tools was developed. SCT also includes programs that provide sequence-based estimates of protein volume (either incorporating hydration or not) and add a hydration layer to models for X-ray scattering modelling. The original SCT software, written in Fortran, resulted in the first atomistic scattering structures to be deposited in the Protein Data Bank, and 77 structures for antibodies, complement proteins and anionic oligosaccharides were determined between 1998 and 2014. For the first time, this software is publicly available, alongside an easier-to-use reimplementation of the same algorithms in Python. Both versions of SCT have been released as open-source software under the Apache 2 license and are available for download from https://github.com/dww100/sct.

Published
2015

50. A Dimerization Site at SCR-17/18 in Factor H Clarifies a New Mechanism for Complement Regulatory Control.

Author

Dunne, Orla M., Gao, Xin, Nan, Ruodan, Gor, Jayesh, Adamson, Penelope J., Gordon, David L., Moulin, Martine, Haertlein, Michael, Forsyth, V. Trevor, and Perkins, Stephen J.

Subjects
COMPLEMENT factor H, DIMERIZATION, X-ray scattering, CELL membranes, PICHIA pastoris
Abstract

Complement Factor H (CFH), with 20 short complement regulator (SCR) domains, regulates the alternative pathway of complement in part through the interaction of its C-terminal SCR-19 and SCR-20 domains with host cell-bound C3b and anionic oligosaccharides. In solution, CFH forms small amounts of oligomers, with one of its self-association sites being in the SCR-16/20 domains. In order to correlate CFH function with dimer formation and the occurrence of rare disease-associated variants in SCR-16/20, we identified the dimerization site in SCR-16/20. For this, we expressed, in Pichia pastoris , the five domains in SCR-16/20 and six fragments of this with one-three domains (SCR-19/20, SCR-18/20, SCR-17/18, SCR-16/18, SCR-17 and SCR-18). Size-exclusion chromatography suggested that SCR dimer formation occurred in several fragments. Dimer formation was clarified using analytical ultracentrifugation, where quantitative c(s) size distribution analyses showed that SCR-19/20 was monomeric, SCR-18/20 was slightly dimeric, SCR-16/20, SCR-16/18 and SCR-18 showed more dimer formation, and SCR-17 and SCR-17/18 were primarily dimeric with dissociation constants of ~5 µM. The combination of these results located the SCR-16/20 dimerization site at SCR-17 and SCR-18. X-ray solution scattering experiments and molecular modelling fits confirmed the dimer site to be at SCR-17/18, this dimer being a side-by-side association of the two domains. We propose that the self-association of CFH at SCR-17/18 enables higher concentrations of CFH to be achieved when SCR-19/20 are bound to host cell surfaces in order to protect these better during inflammation. Dimer formation at SCR-17/18 clarified the association of genetic variants throughout SCR-16/20 with renal disease. [ABSTRACT FROM AUTHOR]

Published
2021
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