Biomedical subjects

Susan Lea

Publications and source records attributed to Susan Lea.

7 recordsLinked to original sources

PubMed2005

Hydrophilic domain II of Escherichia coli Dr fimbriae facilitates cell invasion.

Uropathogenic and diarrheal Escherichia coli strains expressing adhesins of the Dr family bind to decay-accelerating factor, invade epithelial cells, preferentially infect children and pregnant women, and may be associated with chronic or recurrent infections. Thus far, no fimbrial domain(s) that facilitates cell invasion has been identified. We used alanine scanning mutagenesis to replace selected amino acids in hydrophilic domain II of the structural fimbrial subunit DraE and evaluated recombinant mutant DraE for attachment, invasion, and intracellular compartmentalization. The mutation of amino acids V28, T31, G33, Q34, T36, and P40 of DraE reduced or abolished HeLa cell invasion but did not affect attachment. Electron micrographs showed a stepwise entry and fusion of vacuoles containing Escherichia coli mutants T36A and Q34A or corresponding beads with lysosomes, whereas vacuoles with wild-type Dr adhesin showed no fusion. Mutants T31A and Q34A, which were deficient in invasion, appeared to display a reduced capacity for clustering decay-accelerating factor. Our findings suggest that hydrophilic domain II may be involved in cell entry. These data are consistent with the interpretation that in HeLa cells the binding and invasion phenotypes of Dr fimbriae may be separated.

Adhesins, Bacterial↗

PubMed2004

Interactions of decay-accelerating factor (DAF) with haemagglutinating human enteroviruses: utilizing variation in primate DAF to map virus binding sites.

A cellular receptor for the haemagglutinating enteroviruses (HEV), and the protein that mediates haemagglutination, is the membrane complement regulatory protein decay accelerating factor (DAF; CD55). Although primate DAF is highly conserved, significant differences exist to enable cell lines derived from primates to be utilized for the characterization of the DAF binding phenotype of human enteroviruses. Thus, several distinct DAF-binding phenotypes of a selection of HEVs (viz. coxsackievirus A21 and echoviruses 6, 7, 11-13, 29) were identified from binding and infection assays using a panel of primate cells derived from human, orang-utan, African Green monkey and baboon tissues. These studies complement our recent determination of the crystal structure of SCR(34) of human DAF [Williams, P., Chaudhry, Y., Goodfellow, I. G., Billington, J., Powell, R., Spiller, O. B., Evans, D. J. & Lea, S. (2003). J Biol Chem 278, 10691-10696] and have enabled us to better map the regions of DAF with which enteroviruses interact and, in certain cases, predict specific virus-receptor contacts.

Amino Acid Sequence↗

PubMed2004

Citizenship in practice.

The idea of citizenship dates back to classical antiquity. It was originally concerned to address legitimacy of occupancy in the public sphere. Our empirical study contributes to the project of developing a social psychology of the citizen by focusing on the dynamics of such membership, specifically rights and identities. The authors briefly describe a number of existing psychological models of the citizen. Drawing on the main theoretical principles of discursive psychology, rather than asking, 'who is the citizen?' in terms of mental states, we suggest a shift in focus to the more social question, 'how do people claim citizenship and to what ends?'. We present an analysis of private letters of complaint that formed part of a larger mixed data set used in a recent research programme centred on disputes over Britain's newer travellers' rights of settlement. Specifically our analysis demonstrates how some of the letter writers generate a basis for claims-making by making relevant a citizenship/ governance alignment of identities. We also demonstrate how the entitlements associated with the category citizen are built up and action-oriented rather than flowing from the (unproblematic) assumption of citizenship. Finally we discuss how citizenship can be used for the purposes of inclusion and exclusion.

Civil Rights↗

PubMed2003

Rev binds specifically to a purine loop in the SL1 region of the HIV-1 leader RNA.

The leader RNA sequence of human immunodeficiency virus type 1 (HIV-1) consists of a complex series of stem loop structures that are critical for viral replication. Three-dimensional structural analysis by NMR of one of these structures, the SL1 stem loop of the packaging signal region, revealed a highly conserved purine rich loop with a structure nearly identical to the Rev-binding loop of the Rev response element. Using band-shift assays, surface plasmon resonance, and further NMR analysis, we demonstrate that this loop binds Rev. HIV-1 appears to have a second Rev-binding site close to the major splice donor site that may have an additional role in the viral life cycle.

5' Untranslated Regions↗

PubMed2003

Model of the equine rhinitis A virus capsid: identification of a major neutralizing immunogenic site.

Mouse monoclonal antibodies (mAbs) were employed to select neutralization escape mutants of equine rhinitis A virus (ERAV). Amino acid changes in the ERAV mutants resulting in resistance to neutralization were identified in capsid protein VP1 at Lys-114, Pro-240 and Thr-241. Although the changes were located in different parts of the polypeptide chain, these mutants exhibited cross-resistance against all four mAbs employed, indicating that these residues contribute to a single immunogenic site. To explain this result, we constructed a model of the three-dimensional structure of the ERAV capsid based on comparison with the closely related foot-and-mouth disease virus (FMDV O(1)). According to this model, VP1 is folded so that Lys-114 is in the beta E-beta F loop of the polypeptide chain at a considerable distance from Pro-240 and Trp-241 in the C-terminal region. However, around the fivefold axis of symmetry, the C terminus of VP1 in each protomer extends to the beta E-beta F loop of the adjacent VP1 in the next protomer. We therefore propose that the immunogenic site in ERAV is formed as a result of the close proximity of the Lys-114 residue in the beta E-beta F loop of one VP1 molecule and of the Pro-240/Thr-241 residues in the adjacent VP1 polypeptide chain. In terms of the overall architecture of the viral capsid structure, this site in ERAV most closely resembles the immunogenic site 1 of FMDV O(1).

Amino Acid Sequence↗

PubMed2003

Doing cognitive distortions: a discursive psychology analysis of sex offender treatment talk.

Theories of sex offending have for several years relied upon the notion of cognitive distortions as an important cause of sexual offending. In this study we critique this notion and suggest that the sort of phenomenon addressed by cognitive distortions is better understood by adopting a discursive psychology approach. In this approach, talk is regarded as occasioned and action oriented. Thus 'cognitive distortions' are conceptualized as something people do rather than something that people have. Sessions from a prison-based sex offender treatment programme were taped and transcribed. A discursive psychology analysis was conducted on those sessions relating to offenders' first accounts of their offences. Our analysis suggests that offenders utilize a particular narrative organization to manage their blame and responsibility for the offence. This organization is based on a first part which is oriented to quotidian precursors to the offence and an immediately following second which is oriented to a sudden shift in the definition of the situation. The implications of this analysis are discussed, in relation to the status of cognitive distortions and treatment.

Cognition Disorders↗

PubMed2002

Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A.

Decay-accelerating factor (CD55), a regulator of the alternative and classical pathways of complement activation, is expressed on all serum-exposed cells. It is used by pathogens, including many enteroviruses and uropathogenic Escherichia coli, as a receptor prior to infection. We describe the x-ray structure of a pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the three domains required for regulation of human complement. We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55.

Animals↗