Cleavage and serum reactivity of the severe acute respiratory syndrome coronavirus spike protein

Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. S protein could be cleaved by exogenous trypsin but not by coexpressed furin, suggesting that the protein is not normally processed during infection. Reactivity was evident by both flow cytometry and Western blot assays, but the pattern of reactivity varied according to assay and sequence of the antigen. The antibody response to SCoV S protein involves antibodies to both linear and conformational epitopes, with linear epitopes associated with the carboxyl domain and conformational epitopes associated with the amino terminal domain. Recombinant SCoV S protein appears to be a suitable antigen for the development of an efficient and sensitive diagnostic test for SARS, but our data suggest that assay format and choice of S antigen are important considerations.

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove.

Multistep electrochemical reduction path of clusters [Os3(CO)10(α-diimine)]: comparison of electrochemical and photochemical Os-Os(α-diimine) bond cleavage

Electrochemical reduction of the triangular clusters [Os-3(CO)(10)(alpha-dimine)] (alpha-dimine = 2,2'-bipyridine (bpy), 2,2'-bipyrimidine (bpym)) and [Os-3(CO)(10)(mu-bpym) ReBr(CO)(3)] produces primarily the corresponding radical anions. Their stability is strongly determined by the pi acceptor ability of the reducible alpha-dimine ligand, which decreases in the order mu-bpym > bpym >> bpy. Along this series, increasing delocalisation of the odd electron density in the radical anion over the Os(alpha-dimine) chelate ring causes weakening of the axial (CO)(4)Os-Os(CO)(2)(alpha-dimine) bond and its facile cleavage for alpha-diimine = bpy. In contrast, the cluster radical anion is inherently stable for the bridging bpym ligand, the strongest pi-acceptor in the studied series. In the absence of the partial delocalisation of the unpaired electron over the Re( bpym) chelate bond, the Os-3-core of the radical anion remains intact only at low temperatures. Subsequent one-electron reduction of [Os-3(CO)(10)(bpym)](center dot-) at T = 223 K gives the open-triosmium core (= Os-3*) dianion, [Os-3*(CO)(10)(bpym)](2-). Its oxidation leads to the recovery of parent [Os-3(CO)(10)( bpym)]. At room temperature, [Os-3*( CO)(10)(bpym)](2-) is formed along a two-electron (ECE) reduction path. The chemical step (C) results in the formation of an open- core radical anion that is directly reducible at the cathodic potential of the parent cluster in the second electrochemical (E) step. In weakly coordinating tetrahydrofuran, [Os-3*(CO)(10)( bpym)](2-) rapidly attacks yet non- reduced parent cluster molecules, producing the relatively stable open- core dimer [Os-3*(CO)(10)(bpym)](2)(2-) featuring two open- triangle cluster moieties connected with an ( bpym) Os - Os( bpym) bond. In butyronitrile, [Os-3*( CO)(10)(bpym)](2-) is stabilised by the solvent and the dimer [Os-3*(CO)(10)(bpym)](2)(2-) is then mainly formed by reoxidation of the dianion on reverse potential scan. The more reactive cluster [Os-3(CO)(10)(bpy)] follows the same reduction path, as supported by spectroelectrochemical results and additional valuable evidence obtained from cyclic voltammetric scans. The ultimate process in the reduction mechanism is fragmentation of the cluster core triggered by the reduction of the dimer [Os-3*(CO)(10)(alpha- diimine)](2)(2-). The products formed are [Os-2(CO)(8)](2-) and {Os(CO)(2)(alpha- diimine)}(2). The latter dinuclear fragments constitute a linear polymeric chain [Os( CO)(2)(alpha-dimine)] n that is further reducible at the alpha-dimine ligands. For alpha-dimine = bpy, the charged polymer is capable of reducing carbon dioxide. The electrochemical opening of the triosmium core in the [Os-3( CO)(10)(alpha-dimine)] clusters exhibits several common features with their photochemistry. The same Os-alpha-dimine bond dissociates in both cases but the intimate mechanisms are different.

Coordination behavior of pyridylmethylthioether system with cupric chloride and cupric bromide: CS bond cleavage and crystal structures

The coordination behavior of pyridylmethylthioether type of organic moieties having N2S2 donor set [L-1=1,2-bis(2-pyridylmethylthio)ethane, L-2 = 1,3-bis(2-pyridylmethyl-thio)propane and L-3 = 1,4-bis(2-pyridylmethylthio)butane] with copper(II) chloride and copper(II) bromide have been studied in different chemical environments. Copper(II) chloride assisted C-S bond cleavage of the organic moieties leading to the formation of copper(II) picolinate derivatives, whereas, under similar experimental conditions, no C-S bond cleavage was observed in the reaction with copper(II) bromide. The resulted copper(II) complexes isolated from the different mediums have been characterized by spectroscopic and X-ray crystallographic tools.

Societal choice for climate change futures: trees, biotechnology and clean development

The rate and magnitude of predicted climate change require that we urgently mitigate emissions or sequester carbon on a substantial scale in order to avoid runaway climate change. Geo- and bioengineering solutions are increasingly proposed as viable and practical strategies for tackling global warming. Biotechnology companies are already developing transgenic “super carbon-absorbing” trees, which are sold as a cost-effective and relatively low-risk means of sequestering carbon. The question posed in this article is, Do super carbon trees provide real benefits or are they merely a fanciful illusion? It remains unclear whether growing these trees makes sense in terms of the carbon cost of production and the actual storage of carbon. In particular, it is widely acknowledged that “carbon-eating” trees fail to sequester as much carbon as they oxidize and return to the atmosphere; moreover, there are concerns about the biodiversity impacts of large-scale monoculture plantations. The potential social and ecological risks and opportunities presented by such controversial solutions warrant a societal dialogue.

Measuring societal awareness of the rural agrarian landscape: indicators and scale issues

The work presented in this report is part of the effort to define the landscape state and diversity indicator in the frame of COM (2006) 508 “Development of agri-environmental indicators for monitoring the integration of environmental concerns into the common agricultural policy”. The Communication classifies the indicators according to their level of development, which, for the landscape indicator is “in need of substantial improvements in order to become fully operational”. For this reason a full re-definition of the indicator has been carried out, following the initial proposal presented in the frame of the IRENA operation (“Indicator Reporting on the Integration of Environmental Concerns into Agricultural Policy”). The new proposal for the landscape state and diversity indicator is structured in three components: the first concerns the degree of naturalness, the second landscape structure, the third the societal appreciation of the rural landscape. While the first two components rely on a strong bulk of existing literature, the development of the methodology has made evident the need for further analysis of the third component, which is based on a newly proposed top-down approach. This report presents an in-depth analysis of such component of the indicator, and the effort to include a social dimension in large scale landscape assessment.

Priority setting in healthcare: from arbitrariness to societal values

This paper develops an account of the normative basis of priority setting in health care as combining the values which a given society holds for the common good of its members, with the universal provided by a principle of common humanity. We discuss national differences in health basket in Europe and argue that health care decision-making in complex social and moral frameworks is best thought of as anchored in such a principle by drawing on the philosophy of need. We show that health care needs are ethically ‘thick’ needs whose psychological and social construction can best be understood in terms of David Wiggins's notion of vital need: a person's need is vital when failure to meet it leads to their harm and suffering. The moral dimension of priority setting which operates across different societies’ health care systems is located in the demands both of and on any society to avoid harm to its members.

Assessing the impact on chronic disease of incorporating the societal cost of greenhouse gases into the price of food: an econometric and comparative risk assessment modelling study

Objectives To model the impact on chronic disease of a tax on UK food and drink that internalises the wider costs to society of greenhouse gas (GHG) emissions and to estimate the potential revenue. Design An econometric and comparative risk assessment modelling study. Setting The UK. Participants The UK adult population. Interventions Two tax scenarios are modelled: (A) a tax of £2.72/tonne carbon dioxide equivalents (tCO2e)/100 g product applied to all food and drink groups with above average GHG emissions. (B) As with scenario (A) but food groups with emissions below average are subsidised to create a tax neutral scenario. Outcome measures Primary outcomes are change in UK population mortality from chronic diseases following the implementation of each taxation strategy, the change in the UK GHG emissions and the predicted revenue. Secondary outcomes are the changes to the micronutrient composition of the UK diet. Results Scenario (A) results in 7770 (95% credible intervals 7150 to 8390) deaths averted and a reduction in GHG emissions of 18 683 (14 665to 22 889) ktCO2e/year. Estimated annual revenue is £2.02 (£1.98 to £2.06) billion. Scenario (B) results in 2685 (1966 to 3402) extra deaths and a reduction in GHG emissions of 15 228 (11 245to 19 492) ktCO2e/year. Conclusions Incorporating the societal cost of GHG into the price of foods could save 7770 lives in the UK each year, reduce food-related GHG emissions and generate substantial tax revenue. The revenue neutral scenario (B) demonstrates that sustainability and health goals are not always aligned. Future work should focus on investigating the health impact by population subgroup and on designing fiscal strategies to promote both sustainable and healthy diets.

The timing and societal synchronisation of energy demand

It is increasingly important to know about when energy is used in the home, at work and on the move. Issues of time and timing have not featured strongly in energy policy analysis and in modelling, much of which has focused on estimating and reducing total average annual demand per capita. If smarter ways of balancing supply and demand are to take hold, and if we are to make better use of decarbonised forms of supply, it is essential to understand and intervene in patterns of societal synchronisation. This calls for detailed knowledge of when, and on what occasions many people engage in the same activities at the same time, of how such patterns are changing, and of how might they be shaped. In addition, the impact of smart meters and controls partly depends on whether there is, in fact scope for shifting the timing of what people do, and for changing the rhythm of the day. Is the scheduling of daily life an arena that policy can influence, and if so how? The DEMAND Centre has been linking time use, energy consumption and travel diary data as a means of addressing these questions and in this working paper we present some of the issues and results arising from that exercise.

Societal transformation in response to global environmental change: a review of emerging concepts

The study of societal transformation in response to environmental change has become established, yet little consensus exists regarding the conceptual basis of transformation. This paper aims to provide structure to the dialog on transformation, and to reflect on the challenges of social research in this area. Concepts of transformation are identified through a literature review, and examined using four analytical criteria. It is found that the term ‘transformation’ is frequently used merely as a metaphor. When transformation is not used as a metaphor, eight concepts are most frequently employed. They differ with respect to (i) system conceptualization, (ii) notions of social consciousness (deliberate/emergent), and (iii) outcome (prescriptive/descriptive). Problem-based research tends to adopt concepts of deliberate transformation with prescriptive outcome, while concepts of emergent transformation with no prescriptive outcome tend to inform descriptive-analytical research. Dialog around the complementarities of different concepts and their empirical testing are priorities for future research.

The economics of enhanced landfill mining: private and societal performance drivers

This paper addresses the economics of Enhanced Landfill Mining (ELFM) both from a private point of view as well as from a society perspective. The private potential is assessed using a case study for which an investment model is developed to identify the impact of a broad range of parameters on the profitability of ELFM. We found that especially variations in Waste-to-Energy (WtE efficiency, electricity price, CO2-price, WtE investment and operational costs) and ELFM support explain the variation in economic profitability measured by the Internal Rate of Return. To overcome site-specific parameters we also evaluated the regional ELFM potential for the densely populated and industrial region of Flanders (north of Belgium). The total number of potential ELFM sites was estimated using a 5-step procedure and a simulation tool was developed to trade-off private costs and benefits. The analysis shows that there is a substantial economic potential for ELFM projects on the wider regional level. Furthermore, this paper also reviews the costs and benefits from a broader perspective. The carbon footprint of the case study was mapped in order to assess the project’s net impact in terms of greenhouse gas emissions. Also the impacts of nature restoration, soil remediation, resource scarcity and reduced import dependence were valued so that they can be used in future social cost-benefit analysis. Given the complex trade-off between economic, social and environmental issues of ELFM projects, we conclude that further refinement of the methodological framework and the development of the integrated decision tools supporting private and public actors, are necessary.

The EU societal awareness of landscape indicator: a review of its meaning, utility and performance across different scales

There is increasing recognition that agricultural landscapes meet multiple societal needs and demands beyond provision of economic and environmental goods and services. Accordingly, there have been significant calls for the inclusion of societal, amenity and cultural values in agri-environmental landscape indicators to assist policy makers in monitoring the wider impacts of land-based policies. However, capturing the amenity and cultural values that rural agrarian areas provide, by use of such indicators, presents significant challenges. The EU social awareness of landscape indicator represents a new class of generalized social indicator using a top-down methodology to capture the social dimensions of landscape without reference to the specific structural and cultural characteristics of individual landscapes. This paper reviews this indicator in the context of existing agri-environmental indicators and their differing design concepts. Using a stakeholder consultation approach in five case study regions, the potential and limitations of the indicator are evaluated, with a particular focus on its perceived meaning, utility and performance in the context of different user groups and at different geographical scales. This analysis supplements previous EU-wide assessments, through regional scale assessment of the limitations and potentialities of the indicator and the need for further data collection. The evaluation finds that the perceived meaning of the indicator does not vary with scale, but in common with all mapped indicators, the usefulness of the indicator, to different user groups, does change with scale of presentation. This indicator is viewed as most useful when presented at the scale of governance at which end users operate. The relevance of the different sub-components of the indicator are also found to vary across regions.