262 research outputs found

    Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein

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    The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive and nonpermissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the FPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 h postinfection. The wild-type, uninduced phenotype can be rescued by transient expression of FPV184 in FWPVΔ184-infected cells. Ectopic expression of FPV184 inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx1 promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies, capable of suppressing IFN induction early during the next round of infection

    Using the Mechanical Bond to Tune the Performance of a Thermally Activated Delayed Fluorescence Emitter**

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    We report the characterization of rotaxanes based on a carbazole-benzophenone thermally activated delayed fluorescence luminophore. We find that the mechanical bond leads to an improvement in key photophysical properties of the emitter, notably an increase in photoluminescence quantum yield and a decrease in the energy difference between singlet and triplet states, as well as fine tuning of the emission wavelength, a feat that is difficult to achieve when using covalently bound substituents. Computational simulations, supported by X-ray crystallography, suggest that this tuning of properties occurs due to weak interactions between the axle and the macrocycle that are enforced by the mechanical bond. This work highlights the benefits of using the mechanical bond to refine existing luminophores, providing a new avenue for emitter optimization that can ultimately increase the performance of these molecules

    Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

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    Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

    (Q)SAR Modelling of Nanomaterial Toxicity - A Critical Review

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    There is an increasing recognition that nanomaterials pose a risk to human health, and that the novel engineered nanomaterials (ENMs) in the nanotechnology industry and their increasing industrial usage poses the most immediate problem for hazard assessment, as many of them remain untested. The large number of materials and their variants (different sizes and coatings for instance) that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded, and the use of (quantitative) structure activity relationships ((Q)SAR) models as an alternative source of hazard information should be explored. (Q)SAR modelling can be applied to fill the critical knowledge gaps by making the best use of existing data, prioritize physicochemical parameters driving toxicity, and provide practical solutions to the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR technologies to ENMs toxicity prediction, and summarizes the published nano-(Q)SAR studies and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present status of the availability of ENMs characterization/toxicity data, (2) the characterization of nanostructures that meets the need of (Q)SAR analysis, (3) the summary of published nano-(Q)SAR studies and their limitations, (4) the in silico tools for (Q)SAR screening of nanotoxicity and (5) the prospective directions for the development of nano-(Q)SAR models

    Eye movements and their functions in everyday tasks

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    Human saccades and fixations have numerous functions in complex everyday tasks, which have sometimes been neglected in simple experimental situations. In this review I describe some of the characteristics of eye movement behaviour during real-world interactions with objects, while walking in natural environments and while holding a conversation. When performing real-world actions and walking around the world, we fixate relevant features at critical time points during the task. The eye movements between these fixations are planned and coordinated alongside head and body movements, often occurring a short time before the corresponding action. In social interactions, eye movements are both a mechanism for taking in information (for example, when looking at someone?s face or following their gaze) and for signalling one?s attention to another person. Thus eye movements are specific to a particular task context and subject to high-level planning and control during everyday actions

    Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

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    The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG

    Intestinal barrier interactions with specialized CD8 T Cells

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    Copyright: © 2017 Konjar, Ferreira, Blankenhaus and Veldhoen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The trillions of microorganisms that reside in the gastrointestinal tract, essential for nutrient absorption, are kept under control by a single cell barrier and large amounts of immune cells. Intestinal epithelial cells (IECs) are critical in establishing an environment supporting microbial colonization and immunological tolerance. A large population of CD8+ T cells is in direct and constant contact with the IECs and the intraepithelial lymphocytes (IELs). Due to their location, at the interphase of the intestinal lumen and external environment and the host tissues, they seem ideally positioned to balance immune tolerance and protection to preserve the fragile intestinal barrier from invasion as well as immunopathology. IELs are a heterogeneous population, with a large innate-like contribution of unknown specificity, intercalated with antigen-specific tissue-resident memory T cells. In this review, we provide a comprehensive overview of IEL physiology and how they interact with the IECs and contribute to immune surveillance to preserve intestinal homeostasis and host-microbial relationships.Members of the Veldhoen laboratory are supported by European Union H2020 ERA project (N°667824—EXCELLtoINNOV), publication costs were provided by LISBOA-01-0145-FEDER-007391, projeto cofinanciado pelo FEDER através POR Lisboa 2020—Programa Operacional Regional de Lisboa, do PORTUGAL 2020, e pela Fundação para a Ciência e a Tecnologia.info:eu-repo/semantics/publishedVersio

    A review of the distribution of particulate trace elements in urban terrestrial environments and its application to considerations of risk

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    We review the evolution, state of the art and future lines of research on the sources, transport pathways, and sinks of particulate trace elements in urban terrestrial environments to include the atmosphere, soils, and street and indoor dusts. Such studies reveal reductions in the emissions of some elements of historical concern such as Pb, with interest consequently focusing on other toxic trace elements such as As, Cd, Hg, Zn, and Cu. While establishment of levels of these elements is important in assessing the potential impacts of human society on the urban environment, it is also necessary to apply this knowledge in conjunction with information on the toxicity of those trace elements and the degree of exposure of human receptors to an assessment of whether such contamination represents a real risk to the city’s inhabitants and therefore how this risk can be addressed
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