The role of marbling as an intrinsic characteristic at the point of meat purchase – the Taguchi approach

Meat quality is considered a complex concept depending on many characteristics that could be intrinsic or extrinsic. At the same time, intrinsic and extrinsic quality cues affect consumers' purchasing decisions. The importance of each quality cue was analysed and discussed in previous literature. Thus, colour and level of marbling of fresh meat were defined as key quality cues at the point of meat purchase. These characteristics are mostly related to pork and beef. The aim of this study was to identify quality characteristics that most closely match the consumer's preferences and at the same time could be related to quality losses. For that purpose, this paper gives a novel approach of the potential application of Taguchi loss function associated with quality characteristics and related losses for colour and level of marbling. This application can be implemented by providing a quality characteristic's proper target values and limits, which would make the meat production process more consistent

Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe

A portable triaxial cell for beamline imaging of rocks under triaxial state of stress

Acknowledgements The development of the cell was supported by the Research and Teaching Excellence Fund of the School of Engineering, University of Aberdeen. Experiments at BT2, NCNR were supported by UK Engineering and Physical Sciences Research Council grant number EP/N021665/1, NIST and the Physical Measurement Laboratory. Experiments at IMAT were supported by the UK STFC, Experiment number: 1910331 (https://doi.org/10.5286/ISIS.E.RB1910331).Peer reviewedPublisher PD

Mutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma

Background The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. Methodology/Principal Findings Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour. Conclusions/Significance We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy

Use of mRNA- and protein-destabilizing elements to develop a highly responsive reporter system

Reporter assays are widely used in applications that require measurement of changes in gene expression over time (e.g. drug screening). With standard reporter vectors, the measurable effect of a treatment or compound (altered reporter activity) is substantially diluted and delayed, compared with its true effect (altered transcriptional activity). This problem is caused by the relatively long half-lives of both the reporter protein and its mRNA. As a result, the activities of compounds, ligands or treatments that have a relatively minor effect, or a substantial but transient effect, often remain undetected. To circumvent this problem, we introduced modular protein- and mRNA-destabilizing elements into a range of commonly used reporters. Our data show that both elements are required for maximal responses to both increases and decreases in transcriptional activity. The double-destabilized reporter vectors showed markedly improved performance in drug screening, kinetic assays and dose–response titrations

Long-term results after simple versus complex stenting of coronary artery bifurcation lesions:nordic bifurcation study 5-year follow-up results

ObjectivesThis study sought to report the 5-year follow-up results of the Nordic Bifurcation Study.BackgroundRandomized clinical trials with short-term follow-up have indicated that coronary bifurcation lesions may be optimally treated using the optional side branch stenting strategy.MethodsA total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB.ResultsFive-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non–procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (p = 0.15). All-cause death was seen in 5.9% versus 10.4% (p = 0.16) and non–procedure-related myocardial infarction in 4% versus 7.9% (p = 0.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (p = 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (p = 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively.ConclusionsAt 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch

Governing shipping externalities : Baltic ports in the process of SOx emission reduction

This paper analyses the debate which has unfolded in the Baltic Sea Region regarding the reduction of sulphur content in vessel fuels, in order to illustrate how tightening environmental regulation challenges traditional forms of maritime governance. Using an interactive governance approach, this study reconstructs the process of sulphur emission reduction as a complex multi-stakeholder interaction in multiple contexts. The empirical investigation has drawn on documentary material from around the Baltic region, including Russia, and has applied the method of qualitative content analysis. The empirical study focuses on two interlinked questions: (1) How sulphur emission reduction policies are being anticipated by maritime industry, in particular by Baltic ports and (2) How port adaptation strategies are tied into Baltic local and energy contexts. Addressing these questions highlights the role of polycentricity in shipping governance and explains how the same universal international regulations can produce varying patterns of governance. The paper concludes that policy-making shall take an account of the fact that the globalized shipping industry is nevertheless locally and sectorally embedded.Peer reviewe

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND