Phenotypic and genotypic variations within a single bacteriophage species.

Background: Although horizontal gene transfer plays a pivotal role in bacteriophage evolution, many lytic phage genomes are clearly shaped by vertical evolution. We investigated the influence of minor genomic deletions and insertions on various phage-related phenotypic and serological properties. Findings. We collected ten different isolates of Pseudomonas aeruginosa bacteriophage KMV. All sequenced genomes (42-43 kb, long direct terminal repeats) are nearly identical, which intuitively implied strongly similar infections cycles. However, their latent periods vary between 21 and 28 minutes and they are able to lyse between 5 and 58% of a collection of 107 clinical P. aeruginosa strains. We also noted that phages with identical tail structures displayed profound differences in host spectra. Moreover, point mutations in tail and spike proteins were sufficient to evade neutralization by two phage-specific antisera, isolated from rabbits. Conclusion: Although all analyzed phages are 83-97% identical at the genome level, they display a surprisingly large variation in various phenotypic properties. The small overlap in host spectrum and their ability to readily escape immune defences against a nearly identical phage are promising elements for the application of these phages in phage therapy. © 2011 Ceyssens et al; licensee BioMed Central Ltd.


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Testate amoebae as indicators of hydroseral change: an 8,500 year record from Mer Bleue Bog, eastern Ontario, Canada.

Testate amoebae have been used widely as a proxy of hydrological change in ombrotrophic peatlands, although their response to abiotic controls in other types of mire and fenland palaeo-environments is less well understood. This paper examines the response of testate amoebae to hydroseral and other environmental changes at Mer Bleue Bog, Ontario, Canada, a large ombrotrophic peatland, which evolved from a brackish-water embayment in the early Holocene. Sediments, plant macrofossils and diatoms examined from a 5.99 m core collected from the dome of the bog record six stages of development: i) a quiet, brackish-water riverine phase (prior to ca. 8500 cal BP); ii) a shallow lake (ca. 8500–8200 cal BP); iii) fen (8200–7600 cal BP); iv) transitional mire (7600–6900 cal BP); v) pioneer raised mire (6900–4450 cal BP); and vi) ombrotrophic bog (4450 cal BP-present).

Testate amoebae, notably small (<25 µm diameter) specimens of Centropyxis aculeata type, first appear in low abundances in sediments ascribed to the lacustrine phase. Diatoms from the same horizons record a shallowing in water depth, a decline in salinity and the development of emergent macrophytic vegetation, which may have provided favourable conditions for testate amoeba colonization. The testate amoeba communities of the inferred fen phase are more diverse and include centropyxids, cyclopyxids, Arcellidae and Hyalospheniidae, although the assemblages show some differences to those recently reported in modern European fen environments. The Fen–Bog Transition (FBT) is also dominated by C. aculeata type. The change in testate amoeba communities around this key transition is apparent in the results of Detrended Correspondence Analysis (DCA), and appears to reflect a latent nutrient gradient and a secondary moisture gradient. DCA analyses of plant macrofossil remains around the FBT show a similar trend, although the sensitivity of the two proxies to the inferred environmental changes differs. Comparisons with other regional mid-Holocene peatland records confirm the important influence of reduced effective precipitation on the testate amoeba communities during the initiation and development of Sphagnum-dominated, raised bog communities.

Molecular dynamics studies of the STAT3 homodimer:DNA complex: relationships between STAT3 mutations and protein-DNA recognition.

Signal Transducers and Activators of Transcription (STAT) proteins are a group of latent cytoplasmic transcription factors involved in cytokine signaling. STAT3 is a member of the STAT family and is expressed at elevated levels in a large number of diverse human cancers and is now a validated target for anticancer drug discovery.. Understanding the dynamics of the STAT3 dimer interface, accounting for both protein-DNA and protein-protein interactions, with respect to the dynamics of the latent unphosphorylated STAT3 monomer, is important for designing potential small-molecule inhibitors of the activated dimer. Molecular dynamics (MD) simulations have been used to study the activated STAT3 homodimer:DNA complex and the latent unphosphorylated STAT3 monomer in an explicit water environment. Analysis of the data obtained from MD simulations over a 50 ns time frame has suggested how the transcription factor interacts with DNA, the nature of the conformational changes, and ways in which function may be affected. Examination of the dimer interface, focusing on the protein-DNA interactions, including involvement of water molecules, has revealed the key residues contributing to the recognition events involved in STAT3 protein-DNA interactions. This has shown that the majority of mutations in the DNA-binding domain are found at the protein-DNA interface. These mutations have been mapped in detail and related to specific protein-DNA contacts. Their structural stability is described, together with an analysis of the model as a starting-point for the discovery of novel small-molecule STAT3 inhibitors.

Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro.

The potential application of phage therapy for the control of bacterial biofilms has received increasing attention as resistance to conventional antibiotic agents continues to increase. The present study identifies antimicrobial synergy between bacteriophage T4 and a conventional antibiotic, cefotaxime, via standard plaque assay and, importantly, in the in vitro eradication of biofilms of the T4 host strain Escherichia coli 11303. Phage-antibiotic synergy (PAS) is defined as the phenomenon whereby sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacteria's production of virulent phage. Increasing sub-lethal concentrations of cefotaxime resulted in an observed increase in T4 plaque size and T4 concentration. The application of PAS to the T4 one-step growth curve also resulted in an increased burst size and reduced latent period. Combinations of T4 bacteriophage and cefotaxime significantly enhanced the eradication of bacterial biofilms when compared to treatment with cefotaxime alone. The addition of medium (10(4) PFU mL(-1) ) and high (10(7) PFU mL(-1) ) phage titres reduced the minimum biofilm eradication concentration value of cefotaxime against E. coli ATCC 11303 biofilms from 256 to 128 and 32 µg mL(-1) , respectively. Although further investigation is needed to confirm PAS, this study demonstrates, for the first time, that synergy between bacteriophage and conventional antibiotics can significantly improve biofilm control in vitro.

Visualising Textual Knowledge about Risks to Aid Risk Communication

This paper demonstrates a potential application for latent semantic analysis and similar techniques in visualising the differences between two levels of knowledge about a risk issue. The HIV/AIDS risk issue will be examined and the semantic clusters of key words in a technical corpora derived from specific literature about HIV/AIDS will be compared with the semantic clusters of those in more general corpora. It is hoped that these comparisons will create a fast and efficient complementary approach to the articulation of mental models of risk issues that could be used to target possible inconsistencies between expert and lay mental models.

Infection-Responsive Drug Delivery from Urinary Biomaterials Controlled by a Novel Kinetic and Thermodynamic Approach

Purpose. The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve ‘intelligent’ drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.
Methods. p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.
Results. The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH responsive behavior, but additionally exhibited a sustained period of zero-order release.
Conclusions. The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an ‘intelligent’, infection-responsive, self-sterilizing biomaterial.

Understanding the socio-economic distribution of multiple deprivation: An application of self-organising maps

In this paper we seek to contribute to recent efforts to develop and implement multi-dimensional approaches to social exclusion by applying self-organising maps (SOMs) to a set of material deprivation indicators from the Irish component of EU-SILC. The first stage of our analysis involves the identification of sixteen clusters that confirm the multi-dimensional nature of deprivation in contemporary Ireland and the limitations of focusing solely on income. In going beyond this mapping stage, we consider both patterns of socio-economic differentiation in relation to cluster membership and the extent to which such membership contributes to our understanding of economic stress. Our analysis makes clear the continuing importance of traditional forms of stratification relating to factors such as income, social class and housing tenure in accounting for patterns of multiple deprivation. However, it also confirms the role of acute life events and life cycle and location influences. Most importantly, it demonstrates that conclusions relating to the relative impact of different kinds of socio-economic influences are highly dependent on the form of deprivation being considered. Our analysis suggests that debates relating to the extent to which poverty and social exclusion have become individualized should take particular care to distinguish between different kinds of outcomes. Further analysis demonstrates that the SOM approach is considerably more successful than a comparable latent class analysis in identifying those exposed to subjective economic stress. (C) 2010 International Sociological Association Research Committee 28 on Social Stratification and Mobility. Published by Elsevier Ltd. All rights reserved.

Mapping patterns of multiple deprivation using self-organising maps: An application to EU-SILC data for Ireland

The development of conceptual frameworks for the analysis of social exclusion has somewhat out-stripped related methodological developments. This paper seeks to contribute to filling this gap through the application of self-organising maps (SOMs) to the analysis of a detailed set of material deprivation indicators relating to the Irish case. The SOM approach allows us to offer a differentiated and interpretable picture of the structure of multiple deprivation in contemporary Ireland. Employing this approach, we identify 16 clusters characterised by distinct profiles across 42 deprivation indicators. Exploratory analyses demonstrate that, controlling for equivalised household income, SOM cluster membership adds substantially to our ability to predict subjective economic stress. Moreover, in comparison with an analogous latent class approach, the SOM analysis offers considerable additional discriminatory power in relation to individuals' experience of their economic circumstances. The results suggest that the SOM approach could prove a valuable addition to a 'methodological platform' for analysing the shape and form of social exclusion. (c) 2009 Elsevier Inc. All rights reserved.

Comparing poverty and deprivation dynamics:Issues of reliability and validity

In this paper we seek to establish if earlier findings relating to the relationship between income poverty persistence and deprivation persistence could be due to a failure to take measurement error into account. To address this question, we apply a model of dynamics incorporating structural and error components. Our analysis shows a general similarity between latent poverty and deprivation dynamics. In both cases we substantially over-estimate the probability of exiting from poverty or deprivation. We observe a striking similarity across dimensions for both observed and latent outcomes. In both cases levels of poverty and deprivation persistence are higher for the latent case. However, there is no evidence that earlier results relating to the differences in the determinants of poverty and deprivation persistence are a consequence of differential patterns of reliability. Taking measurement error into account seems more likely to accentuate rather than diminish the contrasts highlighted by earlier research. Since longitudinal differences relating to poverty and deprivation cannot be accounted for by measurement error, it seems that we must accept that we are confronted with issues relating to validity rather than reliability. Even where we measure these dimensions over reasonable periods of time and allow for measurement error, they continue to tap relatively distinct phenomenon. Thus, if measures of persistent poverty are to constitute an important component of EU social indicators, a strong case can be made for including parallel measures of deprivation persistence and continuing to explore the relationship between them. © Springer Science+Business Media, Inc. 2006.

Economic vulnerability, multidimensional deprivation and social cohesion in an enlarged European community

In this article we have sought to combine regional and social exclusion perspectives on economic exclusion in the enlarged European Community. Our analysis, based on the European Quality of Life Survey, confirms that while the economically vulnerable, identified through latent class analysis, constitute substantially larger groups in the poorer economic clusters, they are much more sharply differentiated from others in the richer clusters. While the economically vulnerable are also disadvantaged in relation to measures of multidimensional deprivation and social cohesion, between economic clusters differences on these dimensions cannot be accounted for by corresponding variations in levels and intensity of economic vulnerability. In fact, the impact of such vulnerability on social cohesion is greater in the more affluent clusters. Copyright © 2005 SAGE Publications.

Participation of adult mouse bone marrow cells in reconstitution of skin

Results of recent studies have indicated that bone marrow cells can differentiate into various cells of ectodermal, mesodermal, and endodermal origins when transplanted into the body. However, the problems associated with those experiments such as the long latent period, rareness of the event, and difficulty in controlling the processes have hampered detailed mechanistic studies. In the present study, we examined the potency of mouse bone marrow cells to differentiate into cells comprising skin tissues using a skin reconstitution assay. Bone marrow cells from adult green fluorescent protein (GFP)-transgenic mice were transplanted in a mixture of embryonic mouse skin cells (17.5 days post-coitus) onto skin defects made on the backs of nude mice. Within 3 weeks, fully differentiated skin with hair was reconstituted. GFP-positive cells were found in the epidermis, hair follicles, sebaceous glands, and dermis. The localization and morphology of the cells, results of immunohistochemistry, and results of specific staining confirmed that the bone marrow cells had differentiated into epidermal keratinocytes, sebaceous gland cells, follicular epithelial cells, dendritic cells, and endothelial cells under the present conditions. These results indicate that this system is suitable for molecular and cellular mechanistic studies on differentiation of stem cells to various epidermal and dermal cells.

Relations Between Political Violence and Child Adjustment: a four-wave test of the role of emotional insecurity about community

This study further explored the impact of sectarian violence and children's emotional insecurity about community on child maladjustment using a 4-wave longitudinal design. The study included 999 mother-child dyads in Belfast, Northern Ireland (482 boys, 517 girls). Across the 4 waves, child mean age was 12.19 (SD = 1.82), 13.24 (SD = 1.83), 13.61 (SD = 1.99), and 14.66 years (SD = 1.96), respectively. Building on previous studies of the role of emotional insecurity in child adjustment, the current study examines within-person change in emotional insecurity using latent growth curve analyses. The results showed that children's trajectories of emotional insecurity about community were related to risk for developing conduct and emotion problems. These findings controlled for earlier adjustment problems, age, and gender, and took into account the time-varying nature of experience with sectarian violence. Discussion considers the implications for children's emotional insecurity about community for relations between political violence and children's adjustment, including the significance of trajectories of emotional insecurity over time.

The Potency of Pastoral in Hispanic Baroque poetry

This monograph demonstrates that aesthetic and ontological anxieties continue to find diverse expression within the contrived textual artifice of the bucolic space. Drawing upon expansive definitions of the Hispanic literary Baroque, (Beverley, 1980, 2008, Echevarría 1993, Ross 1993, Chemris 2008 , Egido 2009 ) the study analyses the pastoral verse of representative poets of the period to demonstrate that they re-enter an Arcadia that has been defamiliarized but is nonetheless inexorably connected to the classical origins of the mode. Pastoral, in common with other literary forms, is subject to a process of re-evaluation which was latent in its classical legacy. Within the intricacies of this literary construct, surface artistry sustains an effect of artless innocence that is vibrantly contested across the secular, sacred, parodic and colonial text.

It's not that I don't care, I just don't care very much: confounding between attribute non-attendance and taste heterogeneity

With the growing interest in the topic of attribute non-attendance, there is now widespread use of latent class (LC) structures aimed at capturing such behaviour, across a number of different fields. Specifically, these studies rely on a confirmatory LC model, using two separate values for each coefficient, one of which is fixed to zero while the other is estimated, and then use the obtained class probabilities as an indication of the degree of attribute non-attendance. In the present paper, we argue that this approach is in fact misguided, and that the results are likely to be affected by confounding with regular taste heterogeneity. We contrast the confirmatory model with an exploratory LC structure in which the values in both classes are estimated. We also put forward a combined latent class mixed logit model (LC-MMNL) which allows jointly for attribute non-attendance and for continuous taste heterogeneity. Across three separate case studies, the exploratory LC model clearly rejects the confirmatory LC approach and suggests that rates of non-attendance may be much lower than what is suggested by the standard model, or even zero. The combined LC-MMNL model similarly produces significant improvements in model fit, along with substantial reductions in the implied rate of attribute non-attendance, in some cases even eliminating the phenomena across the sample population. Our results thus call for a reappraisal of the large body of recent work that has implied high rates of attribute non-attendance for some attributes. Finally, we also highlight a number of general issues with attribute non-attendance, in particular relating to the computation of willingness to pay measures.

Forecasting Death Rates Using Exogenous Determinants

Mortality models used for forecasting are predominantly based on the statistical properties of time series and do not generally incorporate an understanding of the forces driving secular trends. This paper addresses three research questions: Can the factors found in stochastic mortality-forecasting models be associated with real-world trends in health-related variables? Does inclusion of health-related factors in models improve forecasts? Do resulting models give better forecasts than existing stochastic mortality models? We consider whether the space spanned by the latent factor structure in mortality data can be adequately described by developments in gross domestic product, health expenditure and lifestyle-related risk factors using statistical techniques developed in macroeconomics and finance. These covariates are then shown to improve forecasts when incorporated into a Bayesian hierarchical model. Results are comparable or better than benchmark stochastic mortality models.