BβArg448Lys polymorphism is associated with altered fibrin clot structure and fibrinolysis in type 2 diabetes

Both type 2 diabetes (T2DM) and Bβ448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BβArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BβArg448Lys on fibrin network characteristics in T2DM. Secondary aims investigated interactions between gender and BβArg448Lys substitution in relation to fibrin clot properties and vascular disease. Genotyping for BβArg448Lys and dynamic clot studies were carried out on 822 T2DM patients enrolled in the Edinburgh Type 2 Diabetes Study. Turbidimetric assays of individual plasma samples analysed fibrin clot characteristics with additional experiments conducted on clots made from purified fibrinogen, further examined by confocal and electron microscopy. Plasma clot lysis time in Bβ448Lys was longer than Bβ448Arg variant (mean ± SD; 763 ± 322 and 719 ± 351 seconds [s], respectively; p<0.05). Clots made from plasma-purified fibrinogen of individuals with Arg/Arg, Arg/Lys and Lys/Lys genotypes showed differences in fibre thickness (46.75 ± 8.07, 38.40 ± 6.04 and 25 ± 4.99 nm, respectively; p<0.001) and clot lysis time (419 ± 64, 442 ± 87 and 517 ± 65 s, respectively; p=0.02), directly implicating the polymorphism in the observed changes. Women with Bβ448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bβ448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies

A novel knowledge repository to support industrial symbiosis

The development of tools and methods supporting the identification of Industrial Symbiosis opportunities is of utmost importance to unlock its full potential. Knowledge repositories have proven to be powerful tools in this sense, but often fail mainly due to poor contextualization of information and lack of general applicability (out of the boundaries of specific areas or projects). In this work, a novel approach to the design of knowledge repositories for Industrial Symbiosis is presented, based on the inclusion and categorization of tacit knowledge as well as on the combination of mimicking and input-output matching approaches. The results of a first usability test of the proposed tool are also illustrated

Teleology and Realism in Leibniz's Philosophy of Science

This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz

Human activity was a major driver of the mid-Holocene vegetation change in southern Cumbria: Implications for the elm decline in the British Isles

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The dramatic decline in elm (Ulmus) across a large swathe of north-west Europe in the mid-Holocene has been ascribed to a number of possible factors, including climate change, human activity and/or pathogens. A major limitation for identifying the underlying cause(s) has been the limited number of high-resolution records with robust geochronological frameworks. Here, we report a multiproxy study of an upland (Blea Tarn) and lowland (Urswick Tarn) landscape in southern Cumbria (British Isles) to reconstruct vegetation change across the elm decline in an area with a rich and well-dated archaeological record to disentangle different possible controls. Here we find a two-stage decline in Ulmus taking place between 6350–6150 and 6050–5850 cal a BP, with the second phase coinciding with an intensification of human activity. The scale of the decline and associated human impact is more abrupt in the upland landscape. We consider it likely that a combination of human impact and disease drove the Ulmus decline within southern Cumbria.This work was funded by a studentship for MJG from the University of Exeter and Sir John Fisher Foundation. Additional funding for 14C dating was from the Cumberland and Westmorland Antiquarian and Archaeological Society (Clare Fell Bursary to MJG), and the Australian Research Council (FL100100195)

A database of microRNA expression patterns in Xenopus laevis

MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences

A population-based cohort study on sun habits and endometrial cancer

Background:No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.Methods:A population-based cohort study of 29 508 women who answered a questionnaire in 1990-92, of whom 24 098 responded to a follow-up enquiry in 2000-02. They were followed for an average of 15.5 years.Results:Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4-0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3-0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5-1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).Conclusion:Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.British Journal of Cancer advance online publication, 23 June 2009; doi:10.1038/sj.bjc.6605149 www.bjcancer.com

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species

Alteration of Forest Structure Modifies the Distribution of Scale Insect, Stigmacoccus garmilleri, in Mexican Tropical Montane Cloud Forests

Stigmacoccus garmilleri Foldi (Hemiptera: Margarodidae) is an ecologically important honeydew-producing scale insect associated with oak trees (Quercus spp.) in highland forests of Veracruz, Mexico. The honeydew exudates of S. garmilleri serve as a significant nutrient source to many species of birds, insects, and sooty molds. Oak trees found in the forest interior, forest edge, and those scattered in pasture areas support scale insect colonies, though the pattern of insect infestations on trees within these varying landscape types has not been elucidated. This study aims to describe the distribution of scale insect infestation and any distinctions in honeydew production based on tree location. Scale insect density, honeydew volume, and sugar concentration were surveyed throughout a continuous landscape that included both patches of forest and scattered pasture trees. In addition, the anal filament through which the honeydew drop is secreted was also measured and was experimentally removed to test and measure regrowth. Scale insect densities on tree trunks were greatest on pasture trees, while intermediate densities were found on trees at the forest edge, and low densities on interior forest trees, suggesting that trees in disturbed areas are more susceptible to scale insect infestation. Trees with small diameters at breast height had significantly higher insect densities than trees with medium to large diameters. Trunk aspect (North, South, East, and West) was not a significant determinant of scale insect density. In forested areas higher densities of scale insects were found at three meters height in comparison to lower heights. Sugar concentrations and drop volumes of honeydew in forest and pasture areas were not significantly different. However, scale-insect anal tubes/filaments were significantly longer in pasture than they were in forests. Sugar concentrations of honeydew appeared to be positively correlated with temperature and negatively correlated with relative humidity. Experiments indicated that anal filaments could grow approximately 4 mm every 24 hours, and average tube growth was significantly faster in pasture than in forest, suggesting that there may be a physiological effect on the insect due to landscape disturbance. The results obtained in this study describe the increases in scale insect infestation of trees with forest disturbance. The effect of these increased scale insect densities on the host tree physiology is still to be resolved

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr