An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Fine sediment reduces vertical migrations of Gammarus pulex (Crustacea: Amphipoda) in response to surface water loss

Surface and subsurface sediments in river ecosystems are recognized as refuges that may promote invertebrate survival during disturbances such as floods and streambed drying. Refuge use is spatiotemporally variable, with environmental factors including substrate composition, in particular the proportion of fine sediment (FS), affecting the ability of organisms to move through interstitial spaces. We conducted a laboratory experiment to examine the effects of FS on the movement of Gammarus pulex Linnaeus (Crustacea: Amphipoda) into subsurface sediments in response to surface water loss. We hypothesized that increasing volumes of FS would impede and ultimately prevent individuals from migrating into the sediments. To test this hypothesis, the proportion of FS (1–2 mm diameter) present within an open gravel matrix (4–16 mm diameter) was varied from 10 to 20% by volume in 2.5% increments. Under control conditions (0% FS), 93% of individuals moved into subsurface sediments as the water level was reduced. The proportion of individuals moving into the subsurface decreased to 74% at 10% FS, and at 20% FS no individuals entered the sediments, supporting our hypothesis. These results demonstrate the importance of reducing FS inputs into river ecosystems and restoring FS-clogged riverbeds, to promote refuge use during increasingly common instream disturbances

The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

This is the final version (corrected proof). The final published version is available from Public Library of Science via the DOI in this recordData Availability: Short reads were submitted to the NCBI’s Sequence Read Archive under accession number SRP154617 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP154617). The ChIPseq data are available from NCBI SRA (sequence read archive) database under accession number PRJNA574873 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA574873&o=acc_s%3Aa).Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)Wellcome TrustUniversity of MacauNational Science Foundation (NSF)Vanderbilt UniversityHoward Hughes Medical Institut

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Assessing bird exclusion effects in a wetland crossed by a railway (Sado estuary, Portugal)

L. Borda-de-Água et al. (eds.), Railway Ecology, Chapter 11, p. 179-195Linear transportation infrastructures may displace wildlife from nearby areas that otherwise would provide adequate habitat conditions. This exclusion effect has been documented in roads, but much less is known about railways. Here we evaluated the potential exclusion effect on birds of a railway crossing a wetland of international importance (Sado Estuary, Portugal). We selected 22 sectors representative of locally available wetland habitats (salt pans, rice paddy fields, and intertidal mudflats); of each, half were located either close to (0–500 m) or far from (500–1500 m) the railway line. Water birds were counted in each sector between December 2012 and October 2015, during two months per season (spring, summer, winter, and autumn) and year, at both low and high tide. We recorded 46 species, of which the most abundant (>70% of individuals) were black-headed gull, greater flamingo, northern shoveler, black-tailed godwit, and lesser black-backed gull. Peak abundances were found in autumn and winter. There was no significant variation between sectors close to and far from the railway in species richness, total abundance, and abundance of the most common species. Some species tended to be most abundant either close to or far from the railway albeit not significantly so but this often varied across the tidal and annual cycles. Overall, our study did not find noticeable exclusion effects of this railway on wetland birds, with spatial variation in abundances probably reflecting habitat selection and daily movement patterns. Information is needed on other study systems to assess the generality of our findingsinfo:eu-repo/semantics/publishedVersio

Quantifying Variability of Avian Colours: Are Signalling Traits More Variable?

Background Increased variability in sexually selected ornaments, a key assumption of evolutionary theory, is thought to be maintained through condition-dependence. Condition-dependent handicap models of sexual selection predict that (a) sexually selected traits show amplified variability compared to equivalent non-sexually selected traits, and since males are usually the sexually selected sex, that (b) males are more variable than females, and (c) sexually dimorphic traits more variable than monomorphic ones. So far these predictions have only been tested for metric traits. Surprisingly, they have not been examined for bright coloration, one of the most prominent sexual traits. This omission stems from computational difficulties: different types of colours are quantified on different scales precluding the use of coefficients of variation. Methodology/Principal Findings Based on physiological models of avian colour vision we develop an index to quantify the degree of discriminable colour variation as it can be perceived by conspecifics. A comparison of variability in ornamental and non-ornamental colours in six bird species confirmed (a) that those coloured patches that are sexually selected or act as indicators of quality show increased chromatic variability. However, we found no support for (b) that males generally show higher levels of variability than females, or (c) that sexual dichromatism per se is associated with increased variability. Conclusions/Significance We show that it is currently possible to realistically estimate variability of animal colours as perceived by them, something difficult to achieve with other traits. Increased variability of known sexually-selected/quality-indicating colours in the studied species, provides support to the predictions borne from sexual selection theory but the lack of increased overall variability in males or dimorphic colours in general indicates that sexual differences might not always be shaped by similar selective forces

Vaccinia Virus Proteins A52 and B14 Share a Bcl-2–Like Fold but Have Evolved to Inhibit NF-κB rather than Apoptosis

Vaccinia virus (VACV), the prototype poxvirus, encodes numerous proteins that modulate the host response to infection. Two such proteins, B14 and A52, act inside infected cells to inhibit activation of NF-κB, thereby blocking the production of pro-inflammatory cytokines. We have solved the crystal structures of A52 and B14 at 1.9 Å and 2.7 Å resolution, respectively. Strikingly, both these proteins adopt a Bcl-2–like fold despite sharing no significant sequence similarity with other viral or cellular Bcl-2–like proteins. Unlike cellular and viral Bcl-2–like proteins described previously, A52 and B14 lack a surface groove for binding BH3 peptides from pro-apoptotic Bcl-2–like proteins and they do not modulate apoptosis. Structure-based phylogenetic analysis of 32 cellular and viral Bcl-2–like protein structures reveals that A52 and B14 are more closely related to each other and to VACV N1 and myxoma virus M11 than they are to other viral or cellular Bcl-2–like proteins. This suggests that a progenitor poxvirus acquired a gene encoding a Bcl-2–like protein and, over the course of evolution, gene duplication events have allowed the virus to exploit this Bcl-2 scaffold for interfering with distinct host signalling pathways

How parents choose to use CAM: a systematic review of theoretical models

Background: Complementary and Alternative Medicine (CAM) is widely used throughout the UK and the Western world. CAM is commonly used for children and the decision-making process to use CAM is affected by numerous factors. Most research on CAM use lacks a theoretical framework and is largely based on bivariate statistics. The aim of this review was to identify a conceptual model which could be used to explain the decision-making process in parental choice of CAM. Methods: A systematic search of the literature was carried out. A two-stage selection process with predetermined inclusion/exclusion criteria identified studies using a theoretical framework depicting the interaction of psychological factors involved in the CAM decision process. Papers were critically appraised and findings summarised. Results: Twenty two studies using a theoretical model to predict CAM use were included in the final review; only one examined child use. Seven different models were identified. The most commonly used and successful model was Andersen's Sociobehavioural Model (SBM). Two papers proposed modifications to the SBM for CAM use. Six qualitative studies developed their own model. Conclusion: The SBM modified for CAM use, which incorporates both psychological and pragmatic determinants, was identified as the best conceptual model of CAM use. This model provides a valuable framework for future research, and could be used to explain child CAM use. An understanding of the decision making process is crucial in promoting shared decision making between healthcare practitioners and parents and could inform service delivery, guidance and policy