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Abstract: Critical loads have been used at both the national and international scale in negotiations of protocols controlling the emissions of sulphur and nitrogen. Further, reductions in these pollutants have increasingly high costs; hence, quantifying the uncertainties in the calculation of critical loads and their exceedances has become increasingly important. The UK uses mass balance modelling techniques to calculate steady-state acidity and nutrient nitrogen critical loads for woodland habitats. The calculation uses data from a wide range of sources and the accuracy of the critical loads are influenced by the accuracy of the input data sets. This paper aims to quantify the uncertainties in the data used. A comparison of the uncertainties derived for UK data and those calculated by other European countries reveals a wide range in the estimates of uncertainty and in the methods used to derive them. Possible reasons for these differences are the different methods used to estimate the uncertainty, the scale at which the uncertainty was assessed and underlying methodological differences. Transparency in the way the uncertainties are derived are necessary for communication between scientists and decision makers. [Copyright &y& Elsevier]

Abstract: Critical loads and exceedances have been used as the basis for negotiation of the Gothenburg Protocol and the National Emissions Ceilings Directive to reduce emissions of sulphur and nitrogen across Europe. Since emissions have already been significantly reduced, the associated cost of further emission reductions is high. In order to define future abatement strategies, policy makers therefore need to understand uncertainties associated with critical load exceedances and interpret them accordingly. Deterministic methods of presenting critical load exceedance, which treat the critical load concept as a set criterion, are well established. Spatially explicit uncertainties in deposition estimates for Wales have recently become available and new ways of presenting information on critical load exceedance are now possible. We explore the utility of partial distributions and inverse cumulative distributions of exceedance data, probability of exceedance and cumulative distribution function by habitat, using Wales as a case study. [Copyright &y& Elsevier]

Members of the NR4A subgroup of the nuclear hormone receptor superfamily have emerged as key transcriptional regulators of proliferation and inflammation. NOR1 constitutes a ligand- independent transcription factor of this subgroup and induces cell proliferation; however, the transcriptional mechanisms underlying this mitogenic role remain to be defined. Here, we demonstrate that the F-box protein SKP2 (S phase kinase-associated protein 2), the substrate-specific receptor of the ubiquitin ligase responsible for the degradation of p27KIP1 through the proteasome pathway, constitutes a direct transcriptional target for NOR1. Mitogen-induced Skp2 expression is silenced in vascular smooth muscle cells (VSMC) isolated from Nor1-deficient mice or transfected with Nor1 siRNA. Conversely, adenovirus- mediated overexpression of NOR1 induces Skp2 expression in VSMC and decreases protein abundance of its target p27. Transient transfection experiments establish that NOR1 transactivates the Skp2 promoter through a nerve growth factor-induced clone B response element (NBRE). Electrophoretic mobility shift and chromatin immunoprecipitation assays further revealed that NOR1 is recruited to this NBRE site in the Skp2 promoter in response to mitogenic stimulation. In vivo Skp2 expression is increased during the proliferative response underlying neointima formation, and this transcriptional induction depends on the expression of NOR1. Finally, we demonstrate that overexpression of Skp2 rescues the proliferative arrest of Nor1-deficient VSMC. Collectively, these results characterize Skp2 as a novel NOR1-regulated target gene and detail a previously unrecognized transcriptional cascade regulating mitogen-induced VSMC proliferation. [ABSTRACT FROM AUTHOR]

Members of the nuclear hormone receptor superfamily function as key transcriptional regulators of inflammation and proliferation in cardiovascular diseases. In addition to the ligand-dependent peroxisome proliferator-activated receptors and liver X receptors, this family of transcription factors includes a large number of orphan receptors, and their role in vascular diseases remains to be investigated. The neuron-derived orphan receptor-1 (NOR1) belongs to the ligand-independent NR4A subfamily, which has been implicated in cell proliferation, differentiation, and apoptosis. In this study, we demonstrate NOR1 expression in vascular smooth muscle cells (SMC) of human atherosclerotic lesions. In response to mitogenic stimulation with platelet-derived growth factor (PDGF), SMC rapidly express NOR1 through an ERK-MAPK-dependent signaling pathway. 5′-Deletion analysis, site-directed mutagenesis, and transactivation experiments demonstrate that PDGF-induced NOR1 expression is mediated through a cAMP-response element-binding protein (CREB)-dependent transactivation of the NOR1 promoter. Consequently, short interfering RNA-mediated depletion of CREB abolished PDGF-induced NOR1 expression in SMC. Furthermore, PDGF induced Ser-133 phosphorylation of CREB and subsequent binding to the CRE sites of the endogenous NOR1 promoter. Functional analysis demonstrated that PDGF induces NOR1 transactivation of its consensus NGFI-B-response elements (NBRE) in SMC. We finally demonstrate that SMC isolated from NOR1-deficient mice exhibit decreased cell proliferation and characterize cyclin D1 and D2 as NOR1 target genes in SMC. These experiments indicate that PDGF-induced NOR1 transcription in SMC is mediated through CREB-dependent transactivation of the NOR1 promoter and further demonstrate that NOR1 functions as a key transcriptional regulator of SMC proliferation. [ABSTRACT FROM AUTHOR]