Human Cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against NK cell cytotoxicity.

The activating receptor, NKG2D, is expressed on a variety of immune effector cells and recognizes divergent families of major histocompatibility complex (MHC) class I-related ligands, including the MIC and ULBP proteins. Infection, stress, or transformation can induce NKG2D ligand expression, resulting in effector cell activation and killing of the ligand-expressing target cell. The human cytomegalovirus (HCMV) membrane glycoprotein, UL16, binds to three of the five known ligands for human NKG2D. UL16 is retained in the endoplasmic reticulum and cis-Golgi apparatus of cells and causes MICB to be similarly retained and stabilized within cells. Coexpression of UL16 markedly reduces cell surface levels of MICB, ULBP1, and ULBP2, and decreases susceptibility to natural killer cell-mediated cytotoxicity. Domain swapping experiments demonstrate that the transmembrane and cytoplasmic domains of UL16 are important for intracellular retention of UL16, whereas the ectodomain of UL16 participates in down-regulation of NKG2D ligands. The intracellular sequestration of NKG2D ligands by UL16 represents a novel HCMV immune evasion mechanism to add to the well-documented viral strategies directed against antigen presentation by classical MHC molecules

Decision support tools for agriculture: Towards effective design and delivery

Decision support tools, usually considered to be software-based, may be an important part of the quest for evidence-based decision-making in agriculture to improve productivity and environmental outputs. These tools can lead users through clear steps and suggest optimal decision paths or may act more as information sources to improve the evidence base for decisions. Yet, despite their availability in a wide range of formats, studies in several countries have shown uptake to be disappointingly low. This paper uses a mixed methods approach to investigate the factors affecting the uptake and use of decision support tools by farmers and advisers in the UK. Through a combination of qualitative interviews and quantitative surveys, we found that fifteen factors are influential in convincing farmers and advisers to use decision support tools, which include usability, cost-effectiveness, performance, relevance to user, and compatibility with compliance demands. This study finds a plethora of agricultural decision support tools in operation in the UK, yet, like other studies, shows that their uptake is low. A better understanding of the fifteen factors identified should lead to more effective design and delivery of tools in the future.This research was funded as part of Defra's Sustainable Intensification Platform (Project Code LM0201). In addition, WJS was funded by Arcadia, LVD was funded by the UK Natural Environment Research Council under the Biodiversity and Ecosystem Service Sustainability (BESS) programme, grant code NE/K015419/1. T.A. was supported by the European Commission's Marie Curie International Incoming Fellowship Programme (PIIF-GA-2011-303221) and the Isaac Newton Trust.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.agsy.2016.09.00

Exploring the spatialities of technological and user re-scripting: The case of decision support tools in UK agriculture

The use of decision support tools on-farm may help to deliver evidence-based guidance to farmers, helping to improve productivity and prevent environmental degradation. While much research has sought to increase the uptake of decision support tools in practice, largely by identifying desirable characteristics of system design, rather little work has used a spatial lens to investigate how they are actually used. Using Latour’s notion of ‘the script’, this paper looks at the spatialities of technological and user re-scripting associated with the introduction of decision support tools on-farm. Although there is some literature on how technologies may be re-scripted by users, studies concerning decision support tools are more limited. Furthermore, while there are studies about how technology (not decision support tools) re-scripts agricultural societies, these are generally concerned with macro-level impacts (e.g. labour changes), rather than exploring life on individual farms. This paper, therefore, focuses on exploring the spatialities of re-scripting, investigating how tools themselves are co-constituted in various ways by different users in different spaces, but more particularly on how life on the farm may be changed by the introduction of decision tools. A case study of decision support tool use on farms in England and Wales demonstrates the need to explore spaces on individual farms if we wish to understand processes occurring at the interface between tools and farmers. Firstly, situated knowledge held by farmers and advisers leads to resistance, negotiation, and re-scripting of decision support tools, which are perceived to provide the ‘view from nowhere’. Secondly, the introduction of decision support tools changes the workflows of farmers, affecting how and when they interact with different spaces of their farm. In signalling the need for more research to theorise the spatialities of re-scripting, we briefly explore how our work can inform policy and the development of decision support tools

Truncated Schwinger-Dyson Equations and Gauge Covariance in QED3

We study the Landau-Khalatnikov-Fradkin transformations (LKFT) in momentum space for the dynamically generated mass function in QED3. Starting from the Landau gauge results in the rainbow approximation, we construct solutions in other covariant gauges. We confirm that the chiral condensate is gauge invariant as the structure of the LKFT predicts. We also check that the gauge dependence of the constituent fermion mass is considerably reduced as compared to the one obtained directly by solving SDE.Comment: 17 pages, 11 figures. v3. Improved and Expanded. To appear in Few Body System

Exploring the spatialities of technological and user re-scripting: The case of decision support tools in UK agriculture

The use of decision support tools on-farm may help to deliver evidence-based guidance to farmers, helping to improve productivity and prevent environmental degradation. While much research has sought to increase the uptake of decision support tools in practice, largely by identifying desirable characteristics of system design, rather little work has used a spatial lens to investigate how they are actually used. Using Latour’s notion of ‘the script’, this paper looks at the spatialities of technological and user re-scripting associated with the introduction of decision support tools on-farm. Although there is some literature on how technologies may be re-scripted by users, studies concerning decision support tools are more limited. Furthermore, while there are studies about how technology (not decision support tools) re-scripts agricultural societies, these are generally concerned with macro-level impacts (e.g. labour changes), rather than exploring life on individual farms. This paper, therefore, focuses on exploring the spatialities of re-scripting, investigating how tools themselves are co-constituted in various ways by different users in different spaces, but more particularly on how life on the farm may be changed by the introduction of decision tools. A case study of decision support tool use on farms in England and Wales demonstrates the need to explore spaces on individual farms if we wish to understand processes occurring at the interface between tools and farmers. Firstly, situated knowledge held by farmers and advisers leads to resistance, negotiation, and re-scripting of decision support tools, which are perceived to provide the ‘view from nowhere’. Secondly, the introduction of decision support tools changes the workflows of farmers, affecting how and when they interact with different spaces of their farm. In signalling the need for more research to theorise the spatialities of re-scripting, we briefly explore how our work can inform policy and the development of decision support tools

Strengthen causal models for better conservation outcomes for human well-being

This is the final version. Available from the publisher via the DOI in this record.All data files are available on github at www.github.com/scheng87/ toc.Background Understanding how the conservation of nature can lead to improvement in human conditions is a research area with significant growth and attention. Progress towards effective conservation requires understanding mechanisms for achieving impact within complex social-ecological systems. Causal models are useful tools for defining plausible pathways from conservation actions to impacts on nature and people. Evaluating the potential of different strategies for delivering co-benefits for nature and people will require the use and testing of clear causal models that explicitly define the logic and assumptions behind cause and effect relationships. Objectives and methods In this study, we outline criteria for credible causal models and systematically evaluated their use in a broad base of literature (~1,000 peer-reviewed and grey literature articles from a published systematic evidence map) on links between nature-based conservation actions and human well-being impacts. Results Out of 1,027 publications identified, only ~20% of articles used any type of causal models to guide their work, and only 14 total articles fulfilled all criteria for credibility. Articles rarely tested the validity of models with empirical data. Implications Not using causal models risks poorly defined strategies, misunderstanding of potential mechanisms for affecting change, inefficient use of resources, and focusing on implausible efforts for achieving sustainability.Science for Nature and People Partnership (SNAPP)National Institute for Health Research (NIHR

UBR5 is a Novel E3 Ubiquitin Ligase involved in Skeletal Muscle Hypertrophy and Recovery from Atrophy

We have recently identified that a HECT domain E3 ubiquitin ligase, named UBR5, was epigenetically altered (via DNA methylation) after human skeletal muscle hypertrophy, where its gene expression was positively correlated with increased lean leg mass in humans [1]. This was counterintuitive given the well-defined role of other E3 ligase family members, MuRF1 and MAFbx in muscle atrophy. Therefore, in the present study we aimed to investigate this relatively uncharacterised E3 ubiquitin ligase using multiple in-vivo and in-vitro models of skeletal muscle atrophy, injury, recovery from atrophy as well as anabolism and hypertrophy. We report for the first time, that during atrophy evoked by tetrodotoxin (TTX) nerve silencing in rats, the UBR5 promoter was significantly hypomethylated with a concomitant increase in gene expression early (3 & 7 days) after the induction of atrophy. However, at these timepoints larger increases in MuRF1/MAFbx were observed, and UBR5 expression had returned to baseline levels during later atrophy (14 days) where muscle mass loss was greatest. We confirmed an alternate gene expression profile for UBR5 versus MuRF1/MAFbx in a secondary model of atrophy induced by 7 days continuous low frequency electrical stimulation, where UBR5 demonstrated no significant increase, whereas MuRF1/MAFbx were elevated. Further, after partial (52%) recovery of muscle mass following 7 days TTX-cessation, UBR5 was hypomethylated and increased at the gene expression level, while alternately, reductions in gene expression of MuRF1 and MAFbx were observed. To substantiate these gene expression findings, we observed a significant increase in UBR5 protein abundance after full recovery (14 days) of muscle mass from hindlimb unloading (HU) in rats. Aged rats also demonstrated a similar temporal increase in UBR5 protein abundance after recovery from HU. Further, we confirmed significant increases in UBR5 protein during recovery from nerve crush injury in mice at 28 and 45 days, that related to a full recovery of muscle mass between 45-60 days. During anabolism and hypertrophy, UBR5 gene expression increased following an acute bout of mechanical loading in three-dimensional bioengineered mouse muscle in-vitro, and after chronic electrical stimulation-induced hypertrophy in rats in-vivo, without increases in MuRF1/MAFbx. Additionally, increased UBR5 protein abundance was identified following synergist ablation/functional overload (FO)-induced hypertrophy of the plantaris muscle in mice in-vivo, and finally over a 7-day time-course of regeneration in primary human muscle cells in-vitro. Finally, genetic association studies (> 700,000 SNPs) in human cohorts identified that the A alleles of rs10505025 and rs4734621 SNPs were strongly associated with larger cross-sectional area of fast-twitch muscle fibres and favoured strength/power versus endurance/untrained phenotypes. Overall, we suggest that UBR5 is a novel E3 ubiquitin ligase that is alternatively regulated compared to MuRF1/MAFbx, and is elevated during early atrophy (but not later atrophy), recovery, anabolism and hypertrophy in animals in-vivo as well as during human muscle cell regeneration in-vitro. In humans, genetic variations of the UBR5 gene are strongly associated with larger fast-twitch muscle fibres and strength/power performance

Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions