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7. The mechanism of BAM-assisted OMP folding

Author

Higgins, Anna Juman, Radford, Sheena, and Brockwell, David

Subjects
570
Abstract

Outer membrane proteins (OMPs) mediate the survival and pathogenicity of Gram negative bacteria. The biogenesis of these proteins, however, presents problems as they must be transported to, inserted and folded correctly in the outer membrane in the absence of ATP. This problem is resolved by the β-barrel assembly machinery (BAM) complex: a ~203 kDa complex of five proteins (BamA-E) that enables the membrane insertion and folding of substrate OMPs on a physiological timescale. Despite available crystal structures, the mechanism of this vital protein complex remains poorly understood. In this thesis I use a variety of structural and biochemical tools to probe the nature of BAM-assisted OMP folding, particularly the role of BamA dynamics. Successful purification of the intact BAM complex in the detergent DDM allowed the first cryo-electron microscopy structure of the complex to be obtained, at a resolution of 4.9 Å. This reveals the intact BAM complex with BamA in a laterally-open conformation in which the first (β1) and last (β16) strands of the barrel are no longer hydrogen bonded. In addition, biochemical assays provide the first in vitro evidence of the functional importance of BamA lateral gating in OMP folding. These assays demonstrate that in a reconstituted system utilising the BAM complex, inhibiting the lateral gating of BamA by incorporating new disulphide bonds diminishes the ability of BAM to assist substrate folding. This is shown with two different OMP substrates, tOmpA (the β-barrel domain of OmpA) and OmpT. In synthetic lipids, however, the presence of prefolded BamA is sufficient to aid substrate folding and inhibition of lateral gating by disulphide bonding in this case does not diminish the catalytic effect. The results indicate that BamA likely adopts different roles depending on substrate and lipid. Furthermore, this thesis discusses preliminary experiments towards determining the significance of the β-signal: a conserved sequence found towards the C-terminus of OMPs hypothesised to be important for recognition by BamA. The results show that while some mutations may slow the protein's intrinsic folding into the membrane they do not affect the apparent BamA-catalysed folding rate. However, other single amino-acid substitutions appear to incur a large energetic penalty, rendering the protein incapable of adopting its stable β-barrel structure. Combined, the data allow us to begin dissecting the mechanism of BAM-assisted folding of OMPs, particularly the role of BamA in passive membrane destabilization or active lateral opening.

Published
2018

9. Counsellors' experience of being changed by clients : a narrative autoethnographic inquiry

Author

Higgins, Anna-Gret

Subjects
371.4, counsellor professional development, vicarious posttraumatic growth, counselling, counsellors
Abstract

This thesis addresses four research questions: 1. Are counsellors changed by their clients? 2. If so, how do they make meaning of any change? 3. How does the academic literature explain these changes? 4. How do counsellors ensure change is positive?Previous research has largely focused on the negative effects of clients' stories on counsellors. The potentially positive impact is relatively unexplored - despite the fact that research suggests that it is possible for people who directly experience a wide range of traumatic experiences to grow as a result (Tedeschi & Calhoun, 1996). Moreover, a handful of research studies has suggested that it is possible to experience these changes vicariously (Manning-Jones, deTerte & Stephens, 2015). This thesis describes a qualitative research study carried out with eight counsellors who worked either in a hospice (counselling clients experiencing bereavement or illness) or in private practice (counselling clients who had experienced sexual violence). Narrative inquiry and autoethnography were used to collect and analyse counsellors' stories of being changed by their clients and re-presented as poetic representation, visual art and polyvocal texts. The results show that counsellors do indeed share stories of being changed: sometimes for the worse but often for the better. These changes are in the areas of self-perception, interpersonal relationships and life philosophy and are largely consistent with conceptualisations of vicarious posttraumatic growth. However, what drives change is different. In hospice counsellors, mortality awareness is the driver for change; whereas human cruelty and brutality is the driver in counsellors who work with clients who have experienced sexual violence. Counsellors draw on a number of alternative discourses to make meaning of their experience and this reflects different counselling modalities. The counsellors' stories of change may represent personal growth or reflect western metanarratives linked to a quest for identity. These findings are discussed in relation to the training and supervision of practitioners.

Published
2016

15. Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

Author

Lindsay, Colin R., Shaw, Emily C., Blackhall, Fiona, Blyth, Kevin G., Brenton, James D., Chaturvedi, Anshuman, Clarke, Noel, Dick, Craig, Evans, Thomas R.J., Hall, Geoff, Hanby, Andrew M., Harrison, David J., Johnston, Stephen R.D., Mason, Malcolm D., Morton, Dion, Newton-Bishop, Julia, Nicholson, Andrew G., Oien, Karin A., Popat, Sanjay, Rassl, Doris, Sharpe, Rowena, Taniere, Phillipe, Walker, Ian, Wallace, William A., West, Nicholas P., Butler, Rachel, Gonzalez de Castro, David, Griffiths, Mike, Johnson, Peter W.M., Rehal, Pauline, Butler, Samantha, Smith, Matthew, Doak, Rachel, Tanska, Anna, Halford, Graham, James, Lisa, Kotara, Chris, Masson, Gareth, Clokie, Sam, Bell, Jennie, Macdonald, Fiona, De Castro, David Gonzalez, Thompson, Lisa, Mair, Debbie, Lillis, Suzanne, Wren, Dorte, Hollifield, Robert, Dover, Keeda, Maurya, Manisha, Brooks, Damian, Gomez, Belen, Grady, Lisa, Jones, Thomas, Hooper, Chantal, Webster, Daphne, Travis, Jolyon, Ogwuru, Stephanie, Gazdova, Jana, Collins, Denise, Chapman, Elaine, Leavey, Lisa, Proszek, Paula, Hulkki, Sanna, Collins, V.Peter, Ibrahim, Ash, Brown, Kat, Burge, Jo, Burnett, Karen, Devonshire, Ginny, Moseley, Ellen, Haynes, Bev, Hodgkin, Charlotte, Jimenez-linan, Merche, Jones, Linda, Kenyon, Gilly, Mahler-araujo, Betania, Payne, Karen, Piper, Jo, Richardson, Sue, Rytina, Ed, Warren, Anne, Coker, Liz, Godsall, Gemma, Arends, Mark, O’Neill, Amanda, Rintoul, Katy, Goymer, Donna, Taylor, Julie, Matthews, Claire, Bhayani, Harshil, Osalador, Tina, Niwaz, Zakiya, Higgins, Anna, Bamsey, Olivia, Salter, Janine, Renouf, Louise, Noel-Storr, Glenn, Roberts, Helen, Gierejko, Kasia, Knapman, Paola, Wotherspoon, Andrew, Stamp, Gordon, Attygailye, Ayoma, Hazell, Steve, Osin, Peter, Nerurkar, Ash, Francis, Steven, Runde, Marion, Arch, Jo, Chitnis, Xavier, Siu, Bernard, Townsend, Debra, Hennelly, Laura, Taylor, Natalie, Johnson, Bernadette, Banerjee, Susie, Pyle, Lynda, Hamill, Monica, Gyertson, Jenny, George, Angela, Patel, Krishna, Pearce, Karla, Edmonds, Kim, Sarker, Sarah, Eeles, Rosalind, Bancroft, Liz, Thomas, Sarah, Kano, Yukie, Rowland, Lisa, Brooks, Karen, O’brien, Mary, Bhosle, Jaishree, Priest, Kathy, Ayite, Bee, Severn, Jo, Beedham, Helen, Lucas, Nicky, Tye, Kim, Lorentzos, Alison, Webb, Janine, Kerr, Sarah, Corestav, Lisa, Bottero, Diego, Jell, Laura, Thomas, Janet, Marriott, Cheryl, Rajah, Neil, Cole, Andy, Ly, Dieu, Taniere, Philippe, O’sullivan, Brendan, Swift, Clare, Hughes, Frances, Neil, Desley, Hanby, Andrew, Banks, Roz, Ajayi, Dolapo, Barclay, Alison, Bishop, Julia Newton, Beirne, Debbie, Bernard, Andrew, Berry, Maxine, Bentley, Jo, Bishop, Tim, Chambers, Amy, Clarke, Jude, Crossley, Anne, Gahir, Narinder, Gibson, Debbie, Good, Rona, Grosios, Konstantina, Harnden, Pat, Hasler, Kate, Hindmarch, Damien, Jackson, Sharon, Johnstone, Colin, Jones, Anne-marie, Lambert, Gil, Lane, Sally, Mcnicholas, Nicola, Millican-Slater, Rebecca, Moriaty, Cath, Newsham, Alex, O’connell, Kara, Ripley, Lisa, Sebag-Montefiore, David, Simpson, Mary, Speirs, Val, Sugden, Joh, Tate, Lauren, Tidswell, Emma, Twelves, Chris, Walker, Christy, Waterhouse, Barry, Waugh, Martin, White, Louise, Wright, Elizabeth, Rogan, Jane, Ashton, Garry, Abbey, Caron, Greenhalgh, Michelle, Nonaka, Daisuke, Shing, Elwyn, Gibbard, Carmen, Burton, Georgina, Fawkes, Naomi, Marsden, Angela, Waddington, Rachael, Harrison, Phil, Moghadam, Shahrzad, Murray, Kate, Brown, Sarah, Mitchinson, Christy, Booton, Richard, Shah, Rajesh, Harrison, David, Oniscu, Anca, Wallace, William, Rae, Frances, Marshall, Craig, Mcleod, Linda, Charles, Morag, Sutherland, Sarah Jane, Dawson, Carol, Mitchell, Paul, Maclellan, Alex, Muir, Sandra, Johnstone, Lynne, O’connor, John, Johnstone, Shirley, Mcpherson, Jim, Hair, Jane, Pignatelli, Massimo, Armstrong, Roma, Oien, Karin, Evans, Jeff, Burgoyne, Margaret, Blessing, Karen, Duthie, Fraser, Moyes, Colin, Mallon, Elizabeth, Millan, David, Roberts, Fiona, Seywright, Morag, Fraser, Siobhan, Ford, Ian, Kean, Sharon, Flood, Marion, Grant, David, Mcdonald, Claire, Moffat, Tom, Mclelland, Hugh, Kyle, Alistair, Cameron, Graham, Wright, Martin, Kenny, Stephen, Mcauslan, Karen, Jones, Andrew, Fitzsimons, Ted, Graham, Fiona, Bell, Alexandra, Duffy, Phil, Fisher, Alec, Smith, Alexis, Shannon, Elaine, Woods, Bryan, Hutchison, Colin, Booth, Angela, Duffy, Lyndsay, Mcculloch, Gillian, Sadiq, Hudda, Deakin, Susan, Haywood, Steven, Mason, Malcolm, Chester, John, Parry-jones, Alison, Macarthur, Abby, Williams, Suzanne, Griffiths, David, Morgan, Fiona, and Bailey, Hazel

Published
2018
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17. Conformational restriction shapes inhibition of a multidrug efflux adaptor protein

Author

Lewis, Benjamin Russell, primary, Uddin, Muhammad R., additional, Moniruzzaman, Mohammad, additional, Kuo, Katie M., additional, Higgins, Anna J., additional, Shah, Laila M. N., additional, Sobott, Frank, additional, Parks, Jerry M., additional, Hammerschmid, Dietmar, additional, Gumbart, James C., additional, Zgurskaya, Helen I., additional, and Reading, Eamonn, additional

Published
2022
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19. Labor of Care: Spectacular Fetuses, Healthy, Smart Babies, And Cosmopolitan Pregnancy in Middle Class Beijing

Author

Higgins, Anna Moore

Subjects
Cultural anthropology, China, Embodiment, Gender, Reproduction
Abstract

In early 21st Century Beijing, in the context of the One Child Policy and the developing market economy, middle class women undertook extraordinary measures to have children of the highest possible quality. A baby making industry, comprising private maternity hospitals, providers of prenatal nutrition, imported formula, and supplements, emerged. Women used taijiao, or fetal education, fetal testing and myriad forms of pregnancy management as part of a project of having the smartest, healthiest baby possible. Based on two years of fieldwork in reproductive contexts in Beijing, this dissertation seeks to untangle the complicated relationship between reproduction, state population policies, parents, fetuses, and babies. It argues that the caring labor of hospital workers, sometimes categorized as immaterial, is in fact very much material, in that it creates particular kinds of persons, and that the materiality of this labor demonstrates that material and immaterial are not useful categories. It considers the “non-spectacular” tools of patient education and fetal education alongside spectacular tools of visualization. It argues that technologically assisted reproduction is not exceptional, but rather is on a spectrum with more everyday tools and techniques for influencing pregnancy, such as low-tech educational equipment, stories and metaphors, and fetal education. The dissertation argues that emergent practices of reproduction, specifically the simultaneous use of taijiao and fetal testing, especially the ultrasound, are producing new kinds of fetal personhood, a partial personhood wherein a fetus is both a person and not a person.

Published
2015

20. Transition from child to adult health services for people with learning disabilities: Learning from nurses and families: Transition from child to adult health services

Author

Brown, Michael, Macarthur, Juliet, Higgins, Anna, Truesdale, Maria, and Chouliara, Zoe

Subjects
Learning Disabilities, Transition, Health needs, Complex needs
Abstract

A mixed methods design involving families of young adults with complex learning disabilities and Registered Nurses. The objectives of the study were to: • Investigate and more fully understand the experience of transition between child and adult health services, the challenges involved and the barriers to the provision of person-centred care by obtaining the perspectives of nurses and families as the key stakeholders • Develop best practice strategies in providing person-centred care during transition, embedded in the perspectives of stakeholders • Develop and pilot an on-line learning resource for nurses and other health professionals in practice regarding how effectively manage the transition from child and adult health services for people with learning disabilities and their families.Families of young adults with complex learning disabilities (n=10) who had gone through the transition from child to adults health services in the past year participated in qualitative interviews. Registered Nurses from all Scottish NHS Boards with direct experience of supporting young people with complex learning disabilities were recruited to the study (n=46) and participated in qualitative interviews. An on-line learning resource was developed and piloted in 3 Scottish NHS Boards and follow-up qualitative interviews undertaken with some participants. The findings from the study evidenced that families find the transition process as stressful and at times confusing, with a need for additional support throughout to ensure that care is effectively co-ordinated and care needs planned for. Nurses often play a central role in the care and support of young adults with learning disabilities and are well placed to enable and facilitate the process. Yet some nurses lack confidence and knowledge regarding the specific transition and support needs of young adults with learning disabilities and their families with a need for access to further education. An on-line learning resources was developed and piloted for nurses and other health professionals to enhance their knowledge regarding the care and support needs of young adults with learning disabilities before, during and after the transition from child to adult health services. Seven evidence-based recommendations are made based on the study findings. Conclusion: The population of young adults with learning disabilities is increasing with more living into adulthood with complex health conditions. Many require additional support before, during and after the transition process to ensure is it effective and person and family-centred. Nurses are inn a key position to contribute throughout the transition process.

Published
2021

22. The Curriculum of the University Elementary School

Author

Allen, Anna Elizabeth, Wygant, Elsie A., Port, Elsabeth Vane, Thorne-Thomsen, Gudrun, van Hoesen, Gertrude, Pierce, Catherine, Higgins, Anna, Gillette, Harry Orrin, and Stilwell, Katharine M.

Published
1904

23. The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding.

Author

White, Paul, primary, Haysom, Samuel, additional, Iadanza, Matthew, additional, Higgins, Anna, additional, Machin, Jonathan, additional, Horne, Jim, additional, Schiffrin, Bob, additional, Carpenter-Platt, Charlotte, additional, Whitehouse, James, additional, Storek, Kelly, additional, Rutherford, Steven, additional, Brockwell, David, additional, Ranson, Neil, additional, and Radford, Sheena, additional

Published
2021
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32. 144 The Use of a Multidisciplinary Team Discharge “Huddle” to Improve Patient Flow and Planning

Author

Randles, Mary, primary, Hickey, Sylvia, additional, Cotter, Susanne, additional, Walsh, Carmel, additional, O'Connor, Kieran, additional, O'Sullivan, Catherine, additional, McGrath, Keith, additional, O'Sullivan, Aine, additional, Looney, Eileen, additional, Maher, Sharon, additional, McGuaran, Jane, additional, Higgins, Anna, additional, Quirke, Anne, additional, and Allen, Yvonne, additional

Published
2019
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33. Transitions from child to adult health care for young people with intellectual disabilities: A systematic review:Health transitions and young people with intellectual disabilities

Author

Brown, Michael, Macarthur, Juliet, Higgins, Anna, and Chouliara, Zoe

Subjects
Intellectual disabilities, nursing, systematic review, Nursing(all), complex needs, health services, transitions
Abstract

Aims: To examine the experiences of health transitions for young people with intellectual disabilitiesand their carers and identify the implications for nursing practice.Design: A systematic review and critical appraisal of qualitative, quantitative and mixed methods studies.Data sources: A search of the relevant literature published 2007-2017 was carried out in AMED,ASSIA, CINAHL, MEDLINE, PsycINFO, PubMed and Science Direct Sociological Abstractsdatabases.Review Methods: A total of 12 out of 637 papers identified in the search met the inclusion criteria forthis review. A narrative review of the papers was undertaken by synthesising the key findings and grouping them into concepts and emergent themes.Results: Four main themes were identified: (i) becoming an adult; (ii) fragmented transition process and care; (iii) parents as advocates in emotional turmoil; and (iv) making transitions happen.Conclusion: The range of issues that have an impact on the transition from child to adult health services for young people with intellectual disabilities and their carers raise important implications forpolicy development, nursing practice and education

Published
2019

34. Through the Keyhole

Author

Higgins, Anna

Subjects
Music, Orchestra, Score, Composition
Abstract

Through the Keyhole derives inspiration from the lyrical styles of Tchaikovsky and Rachmaninoff. The transformational form of the piece follows an organic growth process leading up to a true climax. The piece stops, yet it does not end, leaving the listener to feel incomplete. Two melodic themes shape the piece alongside timbral developments. The harmony helps to portray the emotional journey of the piece, changing slightly throughout.

Published
2024

38. PUBLIC EDITOR: Social Media should take on a greater role in Cavalier Daily staff's online engagement

Author

Higgins, Anna

Subjects
Journalists, Journalistic ethics, Social media, Editors, Professional development, News, opinion and commentary, Sports and fitness, Twitter (Online social network)
Abstract

Byline: Anna HigginsAs budding media professionals, student journalists often make a concerted effort to create an online persona to demonstrate their own abilities to engage with readers on multiple platforms. [...]

Published
2019

40. PUBLIC EDITOR: Follow the money in news stories

Author

Higgins, Anna

Subjects
News, opinion and commentary, Sports and fitness, Freedom of Information Act
Abstract

Byline: Anna Higgins Finance at the University -- it's a tricky puzzle that I'm convinced no one person really understands, but we all certainly try. Students, parents, alumni, faculty, staff, [...]

Published
2018

41. The Narrative Forms of Southern Community

Author

Higgins, Anna Dunlap

Subjects
The Narrative Forms of Southern Community (Book), Books -- Book reviews, Arts, visual and performing, Humanities, Regional focus/area studies
Published
2000

42. Transition from child to adult health services: A qualitative study of the views and experiences of families of young adults with intellectual disabilities.

Author

Brown, Michael, Higgins, Anna, and MacArthur, Juliet

Subjects
*CONTINUUM of care, *EXPERIENCE, *INTERVIEWING, *RESEARCH methodology, *MEDICAL care, *PEOPLE with intellectual disabilities, *PARENTS, *QUALITATIVE research, *SOCIAL support, *THEMATIC analysis, *BURDEN of care, *FAMILY attitudes
Abstract

Aims and objectives: To explore the experiences of the families of young adults with intellectual disabilities at the point of transition from child to adult health services. Background: The population of people with intellectual disabilities is changing rapidly, with young people with increasingly complex needs surviving into adulthood and requiring transition from child to adult health services. Design: An interpretative qualitative design. Methods: Semi‐structured interviews were held with ten family carers of young adults with intellectual disabilities and complex care needs, who were in the process of or had recently completed a transition from child to adult health services in Scotland. Data were analysed using thematic analysis. The COREQ checklist was used. Results: Transition emerged as a highly emotional and challenging period for family carers. Their experiences were captured in five main themes: "a deep sense of loss," "an overwhelming process," "parents making transitions happen," "a shock to the adult healthcare system" and "the unbearable pressure." Nurses were often seen as instrumental to counteracting some of these challenges. Conclusions: There is an urgent need to respond to the challenges experienced by carers at the point of transition and beyond, by ensuring early and coordinated planning, effective information sharing and communication and clear transition processes and guidelines. A person‐centred and family‐centred approach is required to minimise negative impact on the health and well‐being of the young adult with intellectual disabilities and their carers. Relevance to clinical practice: Registered nurses have a key role in providing information and support, along with coordinating care at the time of transition from child to adult health services for young adults with complex intellectual disabilities. It is vital that their input is person‐centred and responds effectively to the expert knowledge of family carers, while at the same time ensuring their needs for information and support are also addressed. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Former acting U.S. Attorney General talks 'travel ban,' alleged Russian collusion at Miller Center

Author

Higgins, Anna

Subjects
United States. Department of Justice -- Officials and employees, Attorneys general, Travel, Travel restrictions, Ex-presidents, News, opinion and commentary, Sports and fitness
Abstract

Byline: Anna Higgins Sally Yates, former acting U.S. Attorney General, spoke at the Miller Center Tuesday during a live taping of the center's 'American Forum' program. During the episode, titled [...]

Published
2018

45. Charlottesville city manager appoints interim police chief

Author

Higgins, Anna

Subjects
Police departments, News, opinion and commentary, Sports and fitness
Abstract

Byline: Anna Higgins Charlottesville City Manager Maurice Jones announced former Chesterfield County Police Chief Thierry Dupuis will serve as Charlottesville interim police chief, according to a Wednesday press release. Dupuis [...]

Published
2017

47. Democrats sweep statewide races

Author

Higgins, Anna

Subjects
Political parties, Political campaigns, News, opinion and commentary, Sports and fitness, Democratic Party (United States) -- Political aspects
Abstract

Byline: Anna Higgins Democratic candidates swept Virginia's statewide races Tuesday in a strong showing for the Democratic Party in some of the first major races held since President Donald Trump [...]

Published
2017

49. Board of Visitors votes to remove Confederate plaques from Rotunda

Author

Higgins, Anna

Subjects
News, opinion and commentary, Sports and fitness
Abstract

Byline: Anna Higgins The University's Board of Visitors voted Friday to remove the Confederate plaques erected in 1903 on the Rotunda. The resolution called for the plaques to be moved [...]

Published
2017

50. Cavalier Daily poll shows students differ in opinions regarding BSA demands

Author

Higgins, Anna

Subjects
College students -- Surveys -- Public opinion, White supremacy movements -- Public opinion, News, opinion and commentary, Sports and fitness
Abstract

Byline: Anna Higgins The Cavalier Daily recently conducted a poll of University students to gather data on their thoughts concerning the recent white nationalist violence in Charlottesville, as well as [...]

Published
2017

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