The structure of a reduced form of OxyR from Neisseria meningitidis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - © 2010 Sainsbury et al; licensee BioMed Central Ltd.Background: Survival of the human pathogen, Neisseria meningitidis, requires an effective response to oxidative stress resulting from the release of hydrogen peroxide by cells of the human immune system. In N. meningitidis, expression of catalase, which is responsible for detoxifying hydrogen peroxide, is controlled by OxyR, a redox responsive LysR-type regulator. OxyR responds directly to intracellular hydrogen peroxide through the reversible formation of a disulphide bond between C199 and C208 in the regulatory domain of the protein. Results: We report the first crystal structure of the regulatory domain of an OxyR protein (NMB0173 from N. meningitidis) in the reduced state i.e. with cysteines at positions 199 and 208. The protein was crystallized under reducing conditions and the structure determined to a resolution of 2.4 Å. The overall fold of the Neisseria OxyR shows a high degree of similarity to the structure of a C199S mutant OxyR from E. coli, which cannot form the redox sensitive disulphide. In the neisserial structure, C199 is located at the start of helix α3, separated by 18 Å from C208, which is positioned between helices α3 and α4. In common with other LysR-type regulators, full length OxyR proteins are known to assemble into tetramers. Modelling of the full length neisserial OxyR as a tetramer indicated that C199 and C208 are located close to the dimer-dimer interface in the assembled tetramer. The formation of the C199-C208 disulphide may thus affect the quaternary structure of the protein. Conclusion: Given the high level of structural similarity between OxyR from N. meningitidis and E. coli, we conclude that the redox response mechanism is likely to be similar in both species, involving the reversible formation of a disulphide between C199-C208. Modelling suggests that disulphide formation would directly affect the interface between regulatory domains in an OxyR tetramer which in turn may lead to an alteration in the spacing/orientation of the DNA-binding domains and hence the interaction of OxyR with its DNA binding sites.This work was supported by UK Medical Research Council, the Biotechnology Biological Research Council, and by a MRC Research Studentship

Transnational reflections on transnational research projects on men, boys and gender relations

This article reflects on the research project, ‘Engaging South African and Finnish youth towards new traditions of non-violence, equality and social well-being’, funded by the Finnish and South African national research councils, in the context of wider debates on research, projects and transnational processes. The project is located within a broader analysis of research projects and projectization (the reduction of research to separate projects), and the increasing tendencies for research to be framed within and as projects, with their own specific temporal and organizational characteristics. This approach is developed further in terms of different understandings of research across borders: international, comparative, multinational and transnational. Special attention is given to differences between research projects that are in the Europe and the EU, and projects that are between the global North and the global South. The theoretical, political and practical challenges of the North-South research project are discussed

Radial velocity eclipse mapping of exoplanets

Planetary rotation rates and obliquities provide information regarding the history of planet formation, but have not yet been measured for evolved extrasolar planets. Here we investigate the theoretical and observational perspective of the Rossiter-McLauglin effect during secondary eclipse (RMse) ingress and egress for transiting exoplanets. Near secondary eclipse, when the planet passes behind the parent star, the star sequentially obscures light from the approaching and receding parts of the rotating planetary surface. The temporal block of light emerging from the approaching (blue-shifted) or receding (red-shifted) parts of the planet causes a temporal distortion in the planet's spectral line profiles resulting in an anomaly in the planet's radial velocity curve. We demonstrate that the shape and the ratio of the ingress-to-egress radial velocity amplitudes depends on the planetary rotational rate, axial tilt and impact factor (i.e. sky-projected planet spin-orbital alignment). In addition, line asymmetries originating from different layers in the atmosphere of the planet could provide information regarding zonal atmospheric winds and constraints on the hot spot shape for giant irradiated exoplanets. The effect is expected to be most-pronounced at near-infrared wavelengths, where the planet-to-star contrasts are large. We create synthetic near-infrared, high-dispersion spectroscopic data and demonstrate how the sky-projected spin axis orientation and equatorial velocity of the planet can be estimated. We conclude that the RMse effect could be a powerful method to measure exoplanet spins.Comment: 7 pages, 3 figures, 1 table, accepted for publication in ApJ on 2015 June 1

Mapping of functionalized regions on carbon nanotubes by scanning tunneling microscopy

Scanning tunneling microscopy (STM) gives us the opportunity to map the surface of functionalized carbon nanotubes in an energy resolved manner and with atomic precision. But this potential is largely untapped, mainly due to sample stability issues which inhibit reliable measurements. Here we present a simple and straightforward solution that makes away with this difficulty, by incorporating the functionalized multiwalled carbon nanotubes (MWCNT) into a few layer graphene - nanotube composite. This enabled us to measure energy resolved tunneling conductance maps on the nanotubes, which shed light on the level of doping, charge transfer between tube and functional groups and the dependence of defect creation or functionalization on crystallographic orientation.Comment: Keywords: functionalization, carbon nanotubes, few layer graphene, STM, CITS, ST

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial

© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-

Exploring concepts of health with male prisoners in three category-C English prisons

Lay understandings of health and illness have a well established track record and a plethora of research now exists which has examined these issues. However, there is a dearth of research which has examined the perspectives of those who are imprisoned. This paper attempts to address this research gap. The paper is timely given that calls have been made to examine lay perspectives in different geographical locations and a need to re-examine health promotion approaches in prison settings. Qualitative data from thirty-six male sentenced prisoners from three prisons in England were collected. The data was analysed in accordance with Attride-Stirling's (2001) thematic network approach. Although the men's perceptions of health were broadly similar to the general population, some interesting findings emerged which were directly related to prison life and its associated structures. These included access to the outdoors and time out of their prison cell, as well as maintaining relationships with family members through visits. The paper proposes that prisoners' lay views should be given higher priority given that prison health has traditionally been associated with medical treatment and the bio-medical paradigm more generally. It also suggests that in order to fulfil the World Health Organization's (WHO) vision of viewing prisons as health promoting settings, lay views should be recognised to shape future health promotion policy and practice

Community psychiatric nurses and the care co-ordinator role: squeezed to provide ‘limited nursing’.

Background: The Care Programme Approach (CPA) is the key policy underpinning community-focused mental health services but has been unevenly implemented and is associated with increased inpatient bed use. The care co-ordinator role is central to the CPA and is most often held by Community Psychiatric Nurses (CPNs), but there has been little research into how this role is conducted or how it impacts on the work of CPNs and their ability to meet the needs of service users. Aim: The study aimed to identify and illuminate the factors that either facilitated or constrained the ability of CPNs, in their role as care co-ordinators, to meet service users’ and carers’ needs. Methods: A multiple case study of seven sectorised community mental health teams was employed over two years using predominantly qualitative methods of participant observation, semi-structured interviews and document review. Findings: Additional duties and responsibilities specifically associated with the care co-ordinator role and multidisciplinary working, combined with heavy workloads, combined to produce ‘limited nursing’, whereby CPNs are unable to provide evidence-based psychosocial interventions that are recognised to reduce relapse amongst people with severe mental illness. Conclusions: The role of the CPA care co-ordinator was not designed to support the provision of psychosocial interventions. Consequently, CPNs in the co-ordinator role faced with competing demands are unable to provide the range of structured, evidence-based interventions required. This may partially account for the increased inpatient bed use associated with the CPA

Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling

BACKGROUND: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1–4 status for further clarification of the differing roles for the HER family at a biological level. METHODS: Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (T(pot)). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1–4 status in 55 patients from the BrdU cohort. RESULTS: We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low T(pot )times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. CONCLUSIONS: These results support the hypothesis that HER1–3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role