Subdivision of the bacterioferritin comigratory protein family of bacterial peroxiredoxins based on catalytic activity

Peroxiredoxins are ubiquitous proteins that catalyze the reduction of hydroperoxides, thus conferring resistance to oxidative stress. Using high-resolution mass spectrometry, we recently reclassified one such peroxiredoxin, bacterioferritin comigratory protein (BCP) of Escherichia coli, as an atypical 2-Cys peroxiredoxin that functions through the formation of an intramolecular disulfide bond between the active and resolving cysteine. An engineered E. coli BCP, which lacked the resolving cysteine, retained enzyme activity through a novel catalytic pathway. Unlike the active cysteine, the resolving cysteine of BCP peroxiredoxins is not conserved across all members of the family. To clarify the catalytic mechanism of native BCP enzymes that lack the resolving cysteine, we have investigated the BCP homologue of Burkholderia cenocepacia. We demonstrate that the B. cenocepacia BCP (BcBCP) homologue functions through a 1-Cys catalytic pathway. During catalysis, BcBCP can utilize thioredoxin as a reductant for the sulfenic acid intermediate. However, significantly higher peroxidase activity is observed utilizing glutathione as a resolving cysteine and glutaredoxin as a redox partner. Introduction of a resolving cysteine into BcBCP changes the activity from a 1-Cys pathway to an atypical 2-Cys pathway, analogous to the E. coli enzyme. In contrast to the native B. cenocepacia enzyme, thioredoxin is the preferred redox partner for this atypical 2-Cys variant. BCP-deficient B. cenocepacia exhibit a growth-phase-dependent hypersensitivity to oxidative killing. On the basis of sequence alignments, we believe that BcBCP described herein is representative of the major class of bacterial BCP peroxiredoxins. To our knowledge, this is the first detailed characterization of their catalytic activity. These studies support the subdivision of the BCP family of peroxiredoxins into two classes based on their catalytic activity.

Additional Accommodation Church of St George and St Thomas

A vibrant inner city parish needed space for meetings, language classes, children’s play and other support accommodation as well as a clearer link between the interior of the listed church and the space outside.

The project builds itself about the entrance to the church. The form is manipulated such that the intervention recedes from those entering the church, drawing them into the plan before becoming readable as an addition. The resultant poché between this entrance sequence and the fabric of the church is hollowed out to provide the required accommodation. These rooms are insulated and lined in cork to allow for their use separate to the main body of the church. With budget at a premium the construction methodology was developed from an analysis of traditional Irish boat building techniques, which allowed the use of the solid timber to act as the primary structure with no additional material support.

Constructed in solid walnut the intervention reads with the existing brick interior and yet is clearly identifiable as a contemporary addition.

Aims / Objectives Questions

1 To accommodate new space inside an existing protected structure.
2 To form a new threshold between interior and exterior.
3 To develop an affordable means of construction that would be durable and rapid to erect.
4 To make a contemporary addition in sympathy with the qualities of the existing protect structure, in line with best conservation practice and research.
5 Traditional forms of construction as a model for contemporary technologies.


Principal Investigator: Clancy Moore Architects –Colm Moore

Co-investigator(s): Andrew Clancy, Mathew O’Malley

Funding partner/ Client: Select Vestry of St George and St Thomas

Finance. €35’000

Date (start – finished) Start June 2008 – Completed December 2008

BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage

BRCA1 is a major player in the DNA damage response. This is evident from its loss, which causes cells to become sensitive to a wide variety of DNA damaging agents. The major BRCA1 binding partner, BARD1, is also implicated in the DNA damage response, and recent reports indicate that BRCA1 and BARD1 co-operate in this pathway. In this report, we utilized small interfering RNA to deplete BRCA1 and BARD1 to demonstrate that the BRCA1-BARD1 complex is required for ATM/ATR (ataxia-telangiectasia-mutated/ATM and Rad3-related)-mediated phosphorylation of p53(Ser-15) following IR- and UV radiation-induced DNA damage. In contrast, phosphorylation of a number of other ATM/ATR targets including H2AX, Chk2, Chk1, and c-jun does not depend on the presence of BRCA1-BARD1 complexes. Moreover, prior ATM/ATR-dependent phosphorylation of BRCA1 at Ser-1423 or Ser-1524 regulates the ability of ATM/ATR to phosphorylate p53(Ser-15) efficiently. Phosphorylation of p53(Ser-15) is necessary for an IR-induced G(1)/S arrest via transcriptional induction of the cyclin-dependent kinase inhibitor p21. Consistent with these data, repressing p53(Ser-15) phosphorylation by BRCA1-BARD1 depletion compromises p21 induction and the G(1)/S checkpoint arrest in response to IR but not UV radia-tion. These findings suggest that BRCA1-BARD1 complexes act as an adaptor to mediate ATM/ATR-directed phosphorylation of p53, influencing G(1)/S cell cycle progression after DNA damage.

Government Laws, Regulations and Policies: Small Fish in a Big Pond

Global development has, in recent years, been shaped by the rise of transnational capital. This has implications for the quality and effectiveness of those national laws, regulations and policies in place to monitor transnational capital, ensure that multi national organisations assume responsibility and hold them accountable should they fail to do so. In balancing these objectives, contrasting issues come to the fore, such as the fear of capital flight; an issue especially profound in small open economies where the balance may tip in the favour of retaining, as opposed to regulating, foreign capital.
This paper can be considered in three parts. First, the paper addresses the shift in global leadership from national governments to multinational corporations (with particular reference to the rise of the Transnational Capitalist Class). This shift will incorporate the connotations of the Third Way. In considering this ideology, it will propose the Third Way as a transition phase to a stage when government is more the “third wheel” than an equal partner in governance structures. Second, the implications of the changing nature of governance on the capacity of nation states to develop effective laws, regulations and policies is discussed which leads on to the third aspect of the paper which identifies the challenges for governments, business and society in reimagining the governance structure pertaining to law, regulation and policy and the need to reconsider existing structures in light of global shifts in power structures.
A new leadership structure, both within the national and international governance system has far reaching implications. Boundary constraints no longer an issue, the potential for equality and global democracy is huge. Instead, a post recessionary world faces new governance challenges in the shape of; legitimacy; accountability and responsibility. Capitalism has invaded government and the primary challenge will be in avoiding the same issues that have dogged our financial markets for the last number of years. The challenge then to laws, regulations and public policy is huge, especially considering that the governments regulating are smaller than those dictating agenda on a global level

A direct physiological trade-off between personal and social immunity

1. Recent work shows that organisms possess two strategies of immune response: personal immunity, which defends an individual, and social immunity, which protects other individuals, such as kin. However, it is unclear how individuals divide their limited resources between protecting themselves and protecting others.
2. Here, with experiments on female burying beetles, we challenged the personal immune system and measured subsequent investment in social immunity (antibacterial activity of the anal exudates).
3. Our results show that increased investment in one aspect of personal immunity (wound repair) causes a temporary decrease in one aspect of the social immune response.
4. Our experiments further show that by balancing investment in personal and social immunity in this way during one breeding attempt, females are able to defend their subsequent lifetime reproductive success.
5. We discuss the nature of the physiological trade-off between personal and social immunity in species that differ in the degree of eusociality and coloniality, and suggest that it may also vary within species in relation to age and partner contributions to social immunity.

NF-κB is a critical mediator of BRCA1-induced chemoresistance

BRCA1 mediates resistance to apoptosis in response to DNA-damaging agents, causing BRCA1 wild-type tumours to be significantly more resistant to DNA damage than their mutant counterparts. In this study, we demonstrate that following treatment with the DNA-damaging agents, etoposide or camptothecin, BRCA1 is required for the activation of nuclear factor-?B (NF-?B), and that BRCA1 and NF-?B cooperate to regulate the expression of the NF-?B antiapoptotic targets BCL2 and XIAP. We show that BRCA1 and the NF-?B subunit p65/RelA associate constitutively, whereas the p50 NF-?B subunit associates with BRCA1 only upon DNA damage treatment. Consistent with this BRCA1 and p65 are present constitutively on the promoters of BCL2 and XIAP, whereas p50 is recruited to these promoters only in damage treated cells. Importantly, we demonstrate that the recruitment of p50 onto the promoters of BCL2 and XIAP is dependent upon BRCA1, but independent of its NF-?B partner subunit p65. The functional relevance of NF-?B activation by BRCA1 in response to etoposide and camptothecin is demonstrated by the significantly reduced survival of BRCA1 wild-type cells upon NF-?B inhibition. This study identifies a novel BRCA1-p50 complex, and demonstrates for the first time that NF-?B is required for BRCA1-mediated resistance to DNA damage. It reveals a functional interdependence between BRCA1 and NF-?B, further elucidating the role played by NF-?B in mediating cellular resistance of BRCA1 wild-type tumours to DNA-damaging agents.

Teenage Pregnancy and Motherhood: The Contribution of Support

This paper aims to provide a critical analysis of the role of support in teenage motherhood. Family, partner and peer support are considered and literature emanating from both the USA and UK is reviewed. In summary the research literature indicates that family support is particularly important to teenage mothers and has been found to have a positive influence on parenting behaviours and practices. However, the mother–daughter relationship is not always a straightforward one and conflict between the two can diminish some of the positive impact. The research on partner support highlights how support from fathers and/or other male partners has been linked with improved financial and psychological outcomes for teenage mothers as well as having a positive influence on parenting behaviours. There is also evidence to suggest that support from partners may become increasingly important to teenage mothers over time and can be a valuable source of socializing participation and positive feedback. While the research available on peer support is much more limited it suggests that the emotional support of peers is perceived as being important by teenage mothers. Current research findings suggest that families, partners and peers tend to provide different, but complementary, forms of support for teenage mothers which, on the whole, appear to contribute to more positive outcomes for this group.

Direct, positive feedbacks produce instability in models of interrelationships among soil structure, plants and arbuscular mycorrhizal fungi

Current conceptual models of reciprocal interactions linking soil structure, plants and arbuscular mycorrhizal fungi emphasise positive feedbacks among the components of the system. However, dynamical systems with high dimensionality and several positive feedbacks (i.e. mutualism) are prone to instability. Further, organisms such as arbuscular mycorrhizal fungi (AMF) are obligate biotrophs of plants and are considered major biological agents in soil aggregate stabilization. With these considerations in mind, we developed dynamical models of soil ecosystems that reflect the main features of current conceptual models and empirical data, especially positive feedbacks and linear interactions among plants, AMF and the component of soil structure dependent on aggregates. We found that systems become increasingly unstable the more positive effects with Type I functional response (i.e., the growth rate of a mutualist is modified by the density of its partner through linear proportionality) are added to the model, to the point that increasing the realism of models by adding linear effects produces the most unstable systems. The present theoretical analysis thus offers a framework for modelling and suggests new directions for experimental studies on the interrelationship between soil structure, plants and AMF. Non-linearity in functional responses, spatial and temporal heterogeneity, and indirect effects can be invoked on a theoretical basis and experimentally tested in laboratory and field experiments in order to account for and buffer the local instability of the simplest of current scenarios. This first model presented here may generate interest in more explicitly representing the role of biota in soil physical structure, a phenomenon that is typically viewed in a more process- and management-focused context. (C) 2011 Elsevier Ltd. All rights reserved.

A randomized controlled trial of a self-management psychosocial intervention for men with prostate cancer and their partners: a study protocol.

Background
Little is known about interventions to help men and their partners cope with the after effects of prostate cancer treatment. The lack of in-depth descriptions of the intervention content is hindering the identification of which intervention (or component of an intervention) works.

Aim
To describe the development and evaluation of the content of a self-management psychosocial intervention for men with prostate cancer and their partners.

Design
A feasibility randomized controlled trial including structure, process, and outcome analysis.

Methods
This 9-week intervention commences on completion of treatment and consists of three group and two telephone sessions. The intervention focuses on symptom management, sexual dysfunction, uncertainty management, positive thinking and couple communication. Forty-eight couples will be assigned to either the intervention or a control group receiving usual care. Participants will be assessed at baseline, immediately postintervention and at 1 and 6 months postintervention. Outcome measures for patients and caregivers include self-efficacy, quality of life, symptom distress, uncertainty, benefits of illness, health behaviour, and measures of couple communication and support. An additional caregiver assessment will be completed by the partner.

Discussion
The main purpose of this feasibility study is to investigate the acceptability of the CONNECT programme to men with prostate cancer and their partners and to gain feedback from the participants and facilitators to make changes to and enhance the programme. Reasons why men do not want to participate will be collated to enhance recruitment in the future. We will also test recruitment strategies, randomization procedures, and the acceptability of the questionnaires. Ethical approval granted December 2010.

Accessibility and Health: Towards Walkability Tools for Planning Practice

There is increasing research interest in how we can most effectively intervene in the built environment to change behaviours such as physical activity and improve health. Much of this work has focussed around the concept of walkability and the identification of those attributes of our cities that encourage pedestrian activity, including density, connectivity and the aesthetic of the urban realm (Saelens et al 2003, Frank et al 2010). Much of the existing research has clarified the strength of the relationships between various environmental attributes and the differential impact on different demographic groups (e.g. Panter et al 2011). This has not yet been effectively translated into tools to help integrate the concepts of walkability into decision-making by statutory authorities that can help shape the spatial development and delivery of public services which can support more active lifestyles. A key reason for this has been that standard models for transport planning and accessibility are based on networks of road infrastructure, which provides a weak basis for modelling pedestrian accessibility (Chin et al 2008).

This paper reports the findings of Knowledge Exchange project funded by UK’s Economic and Social Research Council (ES/J010588/1) and partners including Belfast and Derry City Councils and Northern Ireland’s Public Health Agency, the Department of Regional Development and Belfast Healthy Cities, that has attempted to address this problem. This project has mapped city-wide footpath networks and used these to assist partner organisations in developing the evidence base for making decisions on public services based on health impacts and pedestrian access. The paper describes the tool developed, uses a number of examples to highlight its impact on areas of decision-making and evaluates the benefits of further integrating walkability into planning and development practice.

Managing knowledge in internationalizing universities through foreign assignments

Purpose: This article discusses the opportunities presented by the globalization of education and the role of knowledge management in successful global expansion. It seeks to explain why the tacit dimensions of the knowledge transferred during international education provision makes it difficult to provide educational services in offshore campuses, absent the transfer of people. Design/methodology/approach: The article draws on literature in the discipline of international business to explain why internationalizing universities need to consider the role of knowledge transfer as a strategic imperative. As this is a conceptual article, arguments are built on insights from extant theoretical and empirical work. Findings: Based on the analysis of a diverse body of academic literature in the areas of international business, knowledge management and education theory, this article demonstrates the role of foreign assignments in the transfer of tacit knowledge in universities with offshore campuses. Research limitations/implications: The implications of the proposition raised in this article are presented with a focus on how they affirm the need for foreign assignments for effective knowledge management in internationalizing universities. Those implications include the need to use assignments to deliver courses offshore and to create face-to-face interactions with academics at partner universities. Originality/value: Drawing on a diverse body of academic literature, this article provides theoretical and practical insights into how assignments can be utilized in international educational management, international educational delivery, and the creation of an environment in which knowledge resources can be utilized on an international basis. © Emerald Group Publishing Limited.

Promoting multicultural education in the primary classroom:Broadband videoconferencing facilities and digital video

The aim of this study was to explore the impact of interaction (through gathering local field data and engaging in remote reciprocal presentations) on aspects of multicultural awareness. Sixty-six 11-12-year-old Scottish primary school pupils collected data in the field from their local community through questionnaires, interviews, direct observation, digital images and video. From this they distilled a multimedia presentation, delivered by videoconference to a partner school in the USA, who reciprocated. There was some evidence of pre-post project gains in the complexity of the children's perceptions of their community environment, the ethnicity of their community, their own ethnicity, and news images. The children's use of language to define ethnicity also became more complex and their attitudes toward ethnic minorities became more inclusive. The implications for practice, policy and future research were explored. © 2004 Elsevier Ltd. All rights reserved.

Heterogeneity assumptions in the specification of bargaining models: a study of household level trade-offs between commuting time and salary

With many real world decisions being made in conjunction with other decision makers, or single agent decisions having an influence on other members of the decision maker's immediate entourage, there is strong interest in studying the relative weight assigned to different agents in such contexts. In the present paper, we focus on the case of one member of a two person household being asked to make choices affecting the travel time and salary of both members. We highlight the presence of significant heterogeneity across individuals not just in their underlying sensitivities, but also in the relative weight they assign to their partner, and show how this weight varies across attributes. This is in contrast to existing work which uses weights assigned to individual agents at the level of the overall utility rather than for individual attributes. We also show clear evidence of a risk of confounding between heterogeneity in marginal sensitivities and heterogeneity in the weights assigned to each member. We show how this can lead to misleading model results, and argue that this may also explain past results showing bargaining or weight parameters outside the usual [0,1] range in more traditional joint decision making contexts. In terms of substantive results, we find that male respondents place more weight on their partner's travel time, while female respondents place more weight on their partner's salary.

Enhancement of whole cell dioxygenase biotransformations of haloarenes by toxic ionic liquids

Accessing chirally pure cis-diols from arenes using micro-organisms over-expressing toluene dioxygenase (TDO) is now well established, but the conversions remain low for the more toxic and volatile substrates. For such arenes, improved production has already been achieved in the presence of hydrophobic non-toxic ionic liquids (ILs) acting in the form of a reservoir for the arene substrate. Yet, the costs associated with such ILs require extensive process development to render them viable. Herein, we show that optimization of the hydrophobic IL's cationic moiety and of the IL's concentration are key to enhanced conversion yielding between a 2-5 fold yield increase in the conversion of four haloarenes (Ph-X; X = F, Cl, Br, I). Additionally, we report that hydrophilic imidazolium-based ILs offer opportunities to achieve similarly high yielding biotransformations, with further improved reaction rates (<6 h), and this at very low ILs' concentrations (0.0015 V_IL/V_aq). We also demonstrate that the increased biotransformations are due to these ILs being inhibitors of cellular respiration processes and thus favoring the shunting of NADH and O₂ towards the overexpressed biocatalytic process. © 2014 the Partner Organisations.

City visioning and the turn to community:The case of Derry/Londonderry

In the 1980s, urban re-imaging and place marketing were vital elements in the strategies of post-industrial cities aiming to redefine their role, make themselves more competitive and attract global investment and tourists. By the early 1990s, the questionable effects of trickle-down economics on deprived housing estates and the rediscovery of the 'community' as a social partner shifted both the substance and process of vision exercises. This paper examines the experience of building an input into a city vision that aimed to address social and ethno-religious segregation in Derry/Londonderry. Designing a consensus statement for a city that cannot agree its name, was wrecked by bloody violence and has its hinterland fractured by a contested international border, is a difficult and delicate process. The city had a population of 105 800 people in 1998, but is divided by the river Foyle between the mainly Catholic Cityside (to the north and west) and the mainly Protestant Waterside (to the south and east). The analysis connects with the literature on urban policy that emphasises the importance of argumentation and democratic debate in strategic planning and local regeneration (Forester, 1989; Healey, 1996). The paper concludes by arguing that strategies for 'listening' would help to shape a vision that could mobilise community interests around some common urban regional issues and help to promote social and ethno-religious polarisation as mainstream policy concerns.