Pragmatics in legal interpretation

How should pragmatic dimensions of meaning be understood when they occur in the frequently normative use of language in law? In this chapter, referring principally to common law systems, we outline how pragmatic issues arise in the interpretation of legal texts; we describe how legal interpretation has treated indirect and implied meaning; and we ask how far dialogue between linguistic pragmatics and law can enrich thinking and practice in each of these fields

Building and analyzing protein interactome networks by cross-species comparisons

<p>Abstract</p> <p>Background</p> <p>A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast) and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species.</p> <p>Results</p> <p>The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced.</p> <p>Conclusions</p> <p>Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website <url>http://www.interologfinder.org</url> provides research biologists intuitive access to this data.</p

Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the control of scrapie incubation time

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Item not available from this repository.Susceptibility to transmissible spongiform encephalopathies (TSEs) is associated strongly with PrP polymorphisms in humans, sheep and rodents. In mice, scrapie incubation time is controlled by polymorphisms at PrP codons 108 (leucine or phenylalanine) and 189 (threonine or valine), but the precise role of each polymorphism in the control of disease is unknown. The L108F and T189V polymorphisms are present in distinct structural regions of PrP and thus provide an excellent model with which to investigate the role of PrP structure and gene variation in TSEs. Two unique lines of transgenic mice, in which 108F and 189V have been targeted separately into the endogenous murine Prnp a gene, have been produced. TSE inoculation of inbred lines of mice expressing all allelic combinations at codons 108 and 189 has revealed a complex relationship between PrP allele and incubation time. It has been established that both codons 108 and 189 control TSE incubation time, and that each polymorphism plays a distinct role in the disease process. Comparison of ME7 incubation times in mouse lines that are heterozygous at both codons has also identified a previously unrecognized intramolecular interaction between PrP codons 108 and 189.https://doi.org/10.1099/vir.0.80525-086pubpub

The nursing work environment and quality of care: A cross-sectional study using the Essentials of Magnetism II Scale in England

Aims and objectives. To explore the structure of the Essentials of Magnetism II (EOMII) scale using data from nurses working in England; and to describe the impact of different aspects of the nursing work environment on nurse assessed care quality (NACQ). Background. The EOMII Scale was developed in the United States to measure nursing work environments. It has been widely used in the United States and in a number of other countries, but has not yet been used in the United Kingdom. Design. Cross-sectional study. Methods. Registered nurses (n=247) providing direct patient care in two National Health Service hospitals in England completed the EOMII scale and a single-item measuring NACQ. Principal Components Analysis was used to assess the structure of the scale. Correlation and regression analyses were used to describe the relationships between factors and NACQ. Results. A solution with explanatory variance of 45.25% was identified. Forty items loaded on five factors, with satisfactory consistency: i) ward manager support; ii) working as a team; iii) concern for patients; iv) organisational autonomy; and v) constraints on nursing practice. While in univariate analyses each of the factors was significantly associated with NACQ, in multivariate analyses, the relationship between organisational autonomy and NACQ no longer reached significance. However, a multiple mediation model indicated that the effect of organisational autonomy on NACQ was mediated by nurse manager support, working as a team, and concern for patients but not constraints on nursing practice. Conclusions. Subscales of the EOMII identified in an English sample of nurses measured important aspects of the nursing work environment, each of which is related to NACQ. Relevance to clinical practice. The EOMII could be a very useful tool for measuring aspects of the nursing work environment in the English Trusts particularly in relation to the quality of care

Alumoxane/ferroxane nanoparticles for the removal of viral pathogens: the importance of surface functionality to nanoparticle activity

A bi-functional nano-composite coating has been created on a porous Nomex fabric support as a trap for aspirated virus contaminated water. Nomex fabric was successively dip-coated in solutions containing cysteic acid functionalized alumina (alumoxane) nanoparticles and cysteic acid functionalized iron oxide (ferroxane) nanoparticles to form a nanoparticle coated Nomex (NPN) fabric. From SEM and EDX the nanoparticle coating of the Nomex fibers is uniform, continuous, and conformal. The NPN was used as a filter for aspirated bacteriophage MS2 viruses using end-on filtration. All measurements were repeated to give statistical reliability. The NPN fabrics show a large decrease as compared to Nomex alone or alumoxane coated Nomex . An increase in the ferroxane content results in an equivalent increase in virus retention. This suggests that it is the ferroxane that has an active role in deactivating and/or binding the virus. Heating the NPN to 160 C results in the loss of cysteic acid functional groups (without loss of the iron nanoparticleﾒs core structure) and the resulting fabric behaves similar to that of untreated Nomex , showing that the surface functionalization of the nanoparticles is vital for the surface collapse of aspirated water droplets and the absorption and immobilization of the MS2 viruses. Thus, for virus immobilization, it is not sufficient to have iron oxide nanoparticles per se, but the surface functionality of a nanoparticle is vitally important in ensuring efficacy

Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis

Expression of CCL2 (CC chemokine ligand 2) (or monocyte chemoattractant protein-1) regulates inflammatory cell infiltration in the liver and adipose tissue, favouring steatosis. However, its role in the pathogenesis of steatohepatitis is still uncertain. In the present study, we investigated the development of non-alcoholic steatohepatitis induced by an MCD diet (methionine/choline-deficient diet) in mice lacking the CCL2 gene on two different genetic backgrounds, namely Balb/C and C57/Bl6J. WT (wild-type) and CCL2-KO (knockout) mice were fed on a lipid-enriched MCD diet or a control diet for 8 weeks. In Balb/C mice fed on the MCD diet, a lack of CCL2 was associated with lower ALT (alanine transaminase) levels and reduced infiltration of inflammatory cells, together with a lower generation of oxidative-stress-related products. Sirius Red staining demonstrated pericellular fibrosis in zone 3, and image analysis showed a significantly lower matrix accumulation in CCL2-KO mice. This was associated with reduced hepatic expression of TGF-β (transforming growth factor-β), type I procollagen, TIMP-1 (tissue inhibitor of metalloproteinases-1) and α-smooth muscle actin. In contrast, in mice on a C57Bl/6 background, neither ALT levels nor inflammation or fibrosis were significantly different comparing WT and CCL2-KO animals fed on an MCD diet. In agreement, genes related to fibrogenesis were expressed to comparable levels in the two groups of animals. Comparison of the expression of several genes involved in inflammation and repair demonstrated that IL (interleukin)-4 and the M2 marker MGL-1 (macrophage galactose-type C-type lectin 1) were differentially expressed in Balb/C and C57Bl/6 mice. No significant differences in the degree of steatosis were observed in all groups of mice fed on the MCD diet. We conclude that, in experimental murine steatohepatitis, the effects of CCL2 deficiency are markedly dependent on the genetic background

Small-scale indirect plant responses to insect herbivory could have major impacts on canopy photosynthesis and isoprene emission

Insect herbivores cause substantial changes in the leaves they attack, but their effects on the ecophysiology of neighbouring, nondamaged leaves have never been quantified in natural canopies. We studied how winter moth (Operophtera brumata), a common herbivore in temperate forests, affects the photosynthetic and isoprene emission rates of its host plant, the pedunculate oak (Quercus robur). Through a manipulative experiment, we measured leaves on shoots damaged by caterpillars or mechanically by cutting, or left completely intact. To quantify the effects at the canopy scale, we surveyed the extent and patterns of leaf area loss in the canopy. Herbivory reduced photosynthesis both in damaged leaves and in their intact neighbours. Isoprene emission rates significantly increased after mechanical leaf damage. When scaled up to canopy‐level, herbivory reduced photosynthesis by 48 ± 10%. The indirect effects of herbivory on photosynthesis in undamaged leaves (40%) were much more important than the direct effects of leaf area loss (6%). If widespread across other plant–herbivore systems, these findings suggest that insect herbivory has major and previously underappreciated influences in modifying ecosystem carbon cycling, with potential effects on atmospheric chemistry

Motion processing with wide-field neurons in the retino-tecto-rotundal pathway

The retino-tecto-rotundal pathway is the main visual pathway in non-mammalian vertebrates and has been found to be highly involved in visual processing. Despite the extensive receptive fields of tectal and rotundal wide-field neurons, pattern discrimination tasks suggest a system with high spatial resolution. In this paper, we address the problem of how global processing performed by motion-sensitive wide-field neurons can be brought into agreement with the concept of a local analysis of visual stimuli. As a solution to this problem, we propose a firing-rate model of the retino-tecto-rotundal pathway which describes how spatiotemporal information can be organized and retained by tectal and rotundal wide-field neurons while processing Fourier-based motion in absence of periodic receptive-field structures. The model incorporates anatomical and electrophysiological experimental data on tectal and rotundal neurons, and the basic response characteristics of tectal and rotundal neurons to moving stimuli are captured by the model cells. We show that local velocity estimates may be derived from rotundal-cell responses via superposition in a subsequent processing step. Experimentally testable predictions which are both specific and characteristic to the model are provided. Thus, a conclusive explanation can be given of how the retino-tecto-rotundal pathway enables the animal to detect and localize moving objects or to estimate its self-motion parameters

The Gut Microbiome and Aquatic Toxicology: An Emerging Concept for Environmental Health

The microbiome plays an essential role in the health and onset of diseases in all animals, including humans. The microbiome has emerged as a central theme in environmental toxicology, as microbes interact with the host immune system in addition to its role in chemical detoxification. Pathophysiological changes in the gastrointestinal tissue caused by ingested chemicals, and metabolites generated from microbial biodegradation, can lead to systemic adverse effects. This critical review dissects what we know about the impacts of environmental contaminants on the microbiome of aquatic species, with special emphasis on the gut microbiome. We highlight some of the known major gut epithelium proteins in vertebrate hosts that are targets for chemical perturbation, proteins that also directly cross‐talk with the microbiome. These proteins may act as molecular initiators for altered gut function, and we propose a general framework for an adverse outcome pathway that considers gut dysbiosis as a major contributing factor to adverse apical endpoints. We present two case studies, nanomaterials and hydrocarbons with special emphasis on the Deepwater Horizon oil spill, to illustrate how investigations into the microbiome can improve understanding of adverse outcomes. Lastly, we present strategies to functionally relate chemical‐induced gut dysbiosis with adverse outcomes, as this is required to demonstrate cause‐effect relationships. Further investigations into the toxicant‐microbiome relationship may prove to be a major breakthrough for improving animal and human health. This article is protected by copyright. All rights reserve