A small predatory core genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus

Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium Bdellovibrio bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated as members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to gram-negative bacteria, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected, Bacteriovorax shares several characteristic loci with the other delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio that is not conserved among other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be the key indicators of host-interaction predatory-specific processes required for prey entry. The locus from Bdellovibrio bacteriovorus is implicated in the switch from predatory to prey/host-independent growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different families.

The Impact of the Recent Economic Recession on the NEC Contract in Northern Ireland: A Preliminary Study

In comparison to the rest of the United Kingdom (UK) the Northern Irish Construction Industry was disproportionately affected by the recent economic recession. During this period, use of the New Engineering Contract (NEC) has proliferated in the public sector, however no study has been undertaken to examine the impact of the recession on this contract in Northern Ireland. The aim of this paper is to explore NEC contract implementation in Northern Ireland and the impact of the recession on its operation. A qualitative methodology is adopted using a literature review and semi structured interviews with six construction professionals. A qualitative analysis identifies themes and issues arising exploring connections and links between them using thematic coding. The initial findings are that the introduction of the NEC contract in Northern Ireland makes demands of contractors and consultants in terms of additional resources and training. Some consultants show a clear lack of understanding of the contract and its provisions. Whilst there is general agreement that the contract does help to stimulate good project management, the interviewees find the contract time consuming and complicated to administer, describing it as “unforgiving for the architect and unforgiving to the contractor.” Due to the impact of the recession, both contractors and consultants are still reporting a drop in income from pre-recession levels. Project resourcing levels have dropped significantly since the onset of the recession. Adversarial and opportunistic behaviour has increased. Many consultants and contractors are struggling to adequately administer the NEC contract at current income levels. The introduction of the NEC contract and the economic recession have exerted opposing forces on the implementation of the contract, hindering its execution. As the pressures exerted by the economic recession abate and a greater understanding of the contract develops, these opposing forces will ease leading to a more consistent implementation of the contract.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing towards the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement’s effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the SDLP inspired a dialogue with republicanism, encouraging an ongoing re-appraisal within the latter about the nature of Britain’s role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

The Cyrenaican Prehistory Project 2011: Late-Holocene environments and human activity from a cave fill in Cyrenaica, Libya

Little is known about late Holocene environmental change in Cyrenaica. The late Holocene sequence in the Haua Fteah, the key regional site, is highly discontinuous and characterised by stable-burning deposits. The geoarchaeology of the late-Holocene cave fill of a small cave, CP1565, located close to the Haua Fteah, is described. The well-stratified sequence, dating from the fourth century AD to the present day, provides a glimpse of life at the bottom of the settlement hierarchy and of changing environments over the last 1600 years, with degraded vegetation and aridity in the ‘Little Ice Age’.

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.

Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.

Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).

Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.

New exoplanets from the SuperWASP-North survey

We present the current status of the WASP search for transiting exoplanets, focusing on recent planet discoveries from SuperWASP-North and the joint equatorial region (-20≤Dec≤+20) observed by both WASP telescopes. We report the results of monitoring of WASP planets, and discuss how these contribute to our understanding of planet properties and their diversity.

New transiting exoplanets from the SuperWASP-North survey

The Wide Angle Search for Planet (WASP) project is one of the leading projects in the discovery of transiting exoplanets. We present 1) the current status of the WASP-North survey, 2) our recent exoplanet discoveries, and 3) we exemplify how these results fit into our understanding of transiting exoplanet properties and how they can help to understand exoplanet diversity.

Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis

A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis "infectome." These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.

Infrequent Expression of the Cancer-Testis Antigen, PASD1, in Ovarian Cancer

Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue.

Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

The Impact of the Recent Economic Recession on the operation of the NEC Contract in Northern Ireland

In May 2006, the NEC contract was introduced as the preferred contract for Northern Ireland public sector works. This was subsequently followed by the 2007 economic crash and ensuing recession, which continues to affect the Northern Ireland Construction Industry, to a greater extent than the remainder of the United Kingdom (UK). However, use of the NEC contract has increased during this period, particularly in the public sector. There has been debate in the literature regarding the impact of the NEC contract on adversarial behaviour, but little consideration of the impact of external economic factors on the use of the NEC contract. Using a sequential mixed method approach, the study aims to fill this gap in knowledge, through examination of the impact the economic downturn has had on the operation of the NEC contract in Northern Ireland. Qualitative and quantitative findings show that the demands placed by the NEC contract, and the effects of the economic recession, have exerted opposing forces contract implementation, thus hindering its execution. The findings can lead to a deeper understanding, in the context of both industry and academia, of situations where a lack of resources may negatively impact the operation of the NEC contract.