Central Archive at the University of Reading

    Within-host evolution of Staphylococcus aureus during asymptomatic carriage

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    Background Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease

    The curious case of the camelthorn: competition, coexistence and nest-site limitation in a multispecies mutualism

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    Myrmecophyte plants house ants in domatia in exchange for protection from herbivores. Ant-myrmecophyte mutualisms exhibit two general patterns due to competition between ants for plant occupancy: i) domatia nest-sites are a limiting resource and ii) each individual plant hosts one ant species at a time. However, individual camelthorn trees (Vachellia erioloba) typically host two to four ant species simultaneously, often coexisting in adjacent domatia on the same branch. Such fine-grain spatial coexistence brings into question the conventional wisdom on ant-myrmecophyte mutualisms. Camelthorn ants appear not to be nest-site limited, despite low abundance of suitable domatia, and have random distributions of nest-sites within and across trees. These patterns suggest a lack of competition between ants for domatia and contrast strongly with other ant-myrmecophyte systems. Comparison of this unusual case with others suggests that spatial scale is crucial to coexistence or competitive exclusion involving multiple ant species. Furthermore, coexistence may be facilitated when co-occurring ant species diverge strongly on at least one niche axis. Our conclusions provide recommendations for future ant-myrmecophyte research, particularly in utilising multispecies systems to further our understanding of mutualism biology

    Biomimetic and electroactive 3D scaffolds for human neural crest-derived stem cell expansion and osteogenic differentiation

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    Osteoporosis is a skeletal disease characterized by bone loss and bone microarchitectural deterioration. The combination of smart materials and stem cells represents a new therapeutic approach. In the present study, highly porous scaffolds are prepared by combining the conducting polymer PEDOT:PSS with collagen type I, the most abundant protein in bone. The inclusion of collagen proves to be an effective way to modulate their mechanical properties and it induces an increase in scaffolds’ electrochemical impedance. The biomimetic scaffolds support neural crest-derived stem cell osteogenic differentiation, with no need for scaffold pre-conditioning contrarily to other reports

    Callous-unemotional traits, low cortisol reactivity and physical aggression in children: findings from the Wirral Child Health and Development Study

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    Callous-unemotional (CU) traits are thought to confer risk for aggression via reduced amygdala responsivity to distress cues in others. Low cortisol reactivity is thought to confer risk for aggression via reduced arousal and this effect may be confined to boys. We tested the hypothesis that the association between childhood CU traits and aggression would be greatest in the absence of the inhibitory effects of cortisol reactivity, and that this effect would be sex dependent. Participants were 283 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Cortisol reactivity to a social stressor was assessed at 5 years. CU traits were reported by mothers at 5 years, and physical aggression by mothers and teachers at age 7. Results showed that CU traits were associated with elevated aggression at 7 years controlling for earlier aggression. There was no main effect of cortisol reactivity on regression. The association between CU traits and aggression was moderated by cortisol reactivity (p = .011) with a strong association between CU traits and aggression in the presence of low reactivity, and a small and non-significant association in the presence of high reactivity. This association was further moderated by child sex (p = .041) with the joint effect of high CU traits and low cortisol reactivity seen only in boys (p = .016). We report first evidence that a combined deficit in inhibitory processes associated with CU traits and low cortisol reactivity increases risk for childhood aggression, in a sex-dependent manner

    Value co-creation in ICT services company: a case study of a cross-border acquisition

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    Post-merger and acquisition (M&A) integration is especially important for the services industry, where value co-creation between actors plays crucial role. This paper is a qualitative single case study of a multinational company (MNE) in information technology (ICT) industry, and the post-acquisition processes of its subsidiary in Russia. The main contribution of this article is the application of a value co-creation view, which until now has only been applied in the field of service industry research, to the settings of the international business. We also identify the actors and their roles and activities in the value co-creation in the Russian context

    Pathway using WUDAPT's Digital Synthetic City tool towards generating urban canopy parameters for multi-scale urban atmospheric modeling

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    The WUDAPT (World Urban Database and Access Portal Tools project goal is to capture consistent information on urban form and function for cities worldwide that can support urban weather, climate, hydrology and air quality modeling. These data are provided as urban canopy parameters (UCPs) as used by weather, climate and air quality models to simulate the effects of urban surfaces on the overlying atmosphere. Information is stored with different levels of detail (LOD). With higher LOD greater spatial precision is provided. At the lowest LOD, Local Climate Zones(LCZ) with nominal UCP ranges is provided (order 100 m or more). To describe the spatial heterogeneity present in cities with great specificity at different urban scales we introduce the Digital Synthetic City (DSC) tool to generate UCPs at any desired scale meeting the fit-for-purpose goal of WUDAPT. 3D building and road elements of entire city landscapes are simulated based on readily available data. Comparisons with real-world urban data are very encouraging. It is customized (C-DSC) to incorporate each city's unique building morphologies based on unique types, variations and spatial distribution of building typologies, architecture features, construction materials and distribution of green and pervious surfaces. The C-DSC uses crowdsourcing methods and sampling within city Testbeds from around the world. UCP data can be computed from synthetic images at selected grid sizes and stored such that the coded string provides UCP values for individual grid cells

    Balancing act: exploring the tone of The Life Aquatic with Steve Zissou

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    This paper provides an analysis of The Life Aquatic in the context of debates around tone, irony, the Smart Film, the New Sincerity and the Quirky. It argues that Anderson is one of a small but significant number of filmmakers to escape from the indiscriminate irony of fin de sie`cle cinema, and finds The Life Aquatic Aquatic a particularly interesting film in which to explore such matters because of its ready artifice, strong elements of pastiche and measuredly preposterous excesses. Offering a critical analysis, the paper balances an engagement with some of the systemic elements of the film’s tone with the detailed organisation of tonal elements in particular sequences

    Assessing U.S. justifications for using force in response to Syria's chemical attacks: an international law perspective

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    Michael Schmitt and Christopher Ford unpack the Trump Administration’s legal justifications for the April 2017 United States attack on a Syrian airfield in response to its use of chemical weapons against civilians. Schmitt and Ford discuss three possible legal bases for the use of force: self-defense, response to an internationally wrongful act, and humanitarian intervention. The authors conclude that the US’s actions run afoul of limitations in each relevant body of law, and of note, they discuss how this attack is consequential for the validity of humanitarian intervention on another state’s territory without approval from the UN Security Council. They conclude by suggesting that the international community is likely to consider the nature of suffering, in addition to the quantum of suffering, as bearing on the right of States to mount future humanitarian operations

    Motion adaptation and attention: A critical review and meta-analysis

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    The motion aftereffect (MAE) provides a behavioural probe into the mechanisms underlying motion perception, and has been used to study the effects of attention on motion processing. Visual attention can enhance detection and discrimination of selected visual signals. However, the relationship between attention and motion processing remains contentious: not all studies find that attention increases MAEs. Our meta-analysis reveals several factors that explain superficially discrepant findings. Across studies (37 independent samples, 76 effects) motion adaptation was significantly and substantially enhanced by attention (Cohen's d = 1.12, p < .0001). The effect more than doubled when adapting to translating (vs. expanding or rotating) motion. Other factors affecting the attention-MAE relationship included stimulus size, eccentricity and speed. By considering these behavioural analyses alongside neurophysiological work, we conclude that feature-based (rather than spatial, or object-based) attention is the biggest driver of sensory adaptation. Comparisons between naïve and non-naïve observers, different response paradigms, and assessment of 'file-drawer effects' indicate that neither response bias nor publication bias are likely to have significantly inflated the estimated effect of attention
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