Effect of Donor Simvastatin Treatment on Gene Expression Profiles in Human Cardiac Allografts during Ischemia-Reperfusion Injury

Purpose Numerous studies have shown that statin therapy initiated early after heart transplantation has beneficial effects on the development of cardiac allograft vasculopathy. Recently, we were able to show in a randomized clinical trial that simvastatin treatment of brain-dead donors conditions the heart transplant to withstand ischemia-reperfusion injury and to reduce the need for rejection treatments early after transplantation. In this study, we analyzed myocardial gene expression profiles in cardiac allografts after donor simvastatin treatment. Methods 84 heart transplant donors received 80 mg of simvastatin via nasogastric tube (n=42), or no treatment (n=42) in a prospective, double-blinded randomized controlled trial. Transmural Tru-Cut biopsies were taken from the apex of left ventricle of the donor heart immediately before reperfusion and 1 hour after reperfusion. 20 heart biopsies from donors without treatment and 20 heart biopsies from donors with simvastatin treatment will be analyzed with RNA sequencing. Results The preliminary analysis of RNA sequencing data from myocardial biopsies revealed altogether 137 significantly differentially expressed genes in all pairwise comparisons. The overall biological functions of these genes were related to gene ontology terms such as response to toxic substance, leukocyte migration, neutrophil mediated immunity, response to lipopolysaccharide, and response to oxidative stress. At the KEGG pathway level, our results indicated alterations in IL-17, TNF, MAPK and the AGE-RAGE signaling pathways. Conclusion We have shown in previous studies that donor simvastatin treatment induces protective effects against IRI in heart transplant recipients. In this study, we were able to detect significantly differentially expressed genes related to effects of simvastatin treatment. In order to single out genes that show beneficial effects of simvastatin treatment, further analysis will be conducted by exploring gene expression changes in specific biological functional categories, such as interleukin signaling and neutrophil degranulation. The complete analysis will be presented at the ISHLT 2019 congress.Peer reviewe

Multifrequency Observations of the Gamma-Ray Blazar 3C 279 in Low-State during Integral AO-1

We report first results of a multifrequency campaign from radio to hard X-ray energies of the prominent gamma-ray blazar 3C 279 during the first year of the INTEGRAL mission. The variable blazar was found at a low activity level, but was detected by all participating instruments. Subsequently a multifrequency spectrum could be compiled. The individual measurements as well as the compiled multifrequency spectrum are presented. In addition, this 2003 broadband spectrum is compared to one measured in 1999 during a high activity period of 3C 279.Comment: 4 pages including 6 figures, to appear in: 'Proc. of the 5th INTEGRAL Workshop', ESA SP-552, in pres

Triangular-shaped landforms reveal subglacial drainage routes in SW Finland

The aim of this study is to present the first evidence of triangular-shaped till landforms and related erosional features indicative of subglacial drainage within the ice stream bed of the Scandinavian ice sheet in Finland. Previously unidentified grouped patterns of Quaternary deposits with triangular landforms can be recognized from LiDAR-based DEMs. The triangular landforms occur as segments within geomorphologically distinguishable routes that are associated with eskers. The morphological and sedimentological characteristics as well as the distribution of the triangular landforms are interpreted to involve the creep of saturated deforming till, flow and pressure fluctuations of subglacial meltwater associated with meltwater erosion. There are no existing models for the formation of this kind of large-scale drainage systems, but we claim that they represent an efficient drainage system for sub glacial meltwater transfer under high pressure conditions. Our hypothesis is that the routed, large-scale subglacial drainage systems described herein form a continuum between channelized (eskers) and more widely spread small-scale distributed subglacial drainage. Moreover, the transition from the conduit dominated drainage to triangular-shaped subglacial landforms takes place about 50-60 km from the ice margin. We provide an important contribution towards a more realistic representation of ice sheet hydrological drainage systems that could be used to improve paleoglaciological models and to simulate likely responses of ice sheets to increased meltwater production. (C) 2017 Elsevier Ltd. All rights reserved

Spatial structure of the 8200 cal yr BP event in northern Europe

International audienceA synthesis of well-dated high-resolution pollen records suggests a spatial structure in the 8200 cal yr BP event in northern Europe. The temperate, thermophilous tree taxa, especially Corylus, Ulmus, and Alnus, decline abruptly between 8300 and 8000 cal yr BP at most sites located south of 61° N, whereas there is no clear change in pollen values at the sites located in the North-European tree-line region. Pollen-based quantitative temperature reconstructions and several other, independent palaeoclimate proxies, such as lacustrine oxygen-isotope records, reflect the same pattern, with no detectable cooling in the sub-arctic region. The observed patterns challenges the general view of the wide-spread occurrence of the 8200 cal yr BP event in the North Atlantic region. An alternative explanation is that the cooling during the 8200 cal yr BP event took place mostly during the winter and spring, and the ecosystems in the south responded sensitively to the cooling during the onset of the growing season. In contrast, in the sub-arctic area, where the vegetation was still dormant and lakes ice-covered, the cold event is not reflected in pollen-based or lake-sediment-based records

A study of 15N14N isotopic exchange over cobalt molybdenum nitrides

The 14N/15N isotopic exchange pathways over Co3Mo3N, a material of interest as an ammonia synthesis catalyst and for the development of nitrogen transfer reactions, have been investigated. Both the homomolecular and heterolytic exchange processes have been studied, and it has been shown that lattice nitrogen species are exchangeable. The exchange behavior was found to be a strong function of pretreatment with ca. 25% of lattice N atoms being exchanged after 40 min at 600 °C after N2 pretreatment at 700 °C compared to only 6% following similar Ar pretreatment. This observation, for which the potential contribution of adsorbed N species can be discounted, is significant in terms of the application of this material. In the case of the Co6Mo6N phase, regeneration to Co3Mo3N under 15N2 at 600 °C occurs concurrently with 14N15N formation. These observations demonstrate the reactivity of nitrogen in the Co–Mo–N system to be a strong function of pretreatment and worthy of further consideration

Diffraction and Total Cross-Section at the Tevatron and the LHC

At the Tevatron, the total p_bar-p cross-section has been measured by CDF at 546 GeV and 1.8 TeV, and by E710/E811 at 1.8 TeV. The two results at 1.8 TeV disagree by 2.6 standard deviations, introducing big uncertainties into extrapolations to higher energies. At the LHC, the TOTEM collaboration is preparing to resolve the ambiguity by measuring the total p-p cross-section with a precision of about 1 %. Like at the Tevatron experiments, the luminosity-independent method based on the Optical Theorem will be used. The Tevatron experiments have also performed a vast range of studies about soft and hard diffractive events, partly with antiproton tagging by Roman Pots, partly with rapidity gap tagging. At the LHC, the combined CMS/TOTEM experiments will carry out their diffractive programme with an unprecedented rapidity coverage and Roman Pot spectrometers on both sides of the interaction point. The physics menu comprises detailed studies of soft diffractive differential cross-sections, diffractive structure functions, rapidity gap survival and exclusive central production by Double Pomeron Exchange.Peer reviewe

Research note: residential distance and recreational visits to coastal and inland blue spaces in eighteen countries

Varied categorisations of residential distance to bluespace in population health studies make comparisons difficult. Using survey data from eighteen countries, we modelled relationships between residential distance to blue spaces (coasts, lakes, and rivers), and self-reported recreational visits to these environments at least weekly, with penalised regression splines. We observed exponential declines in visit probability with increasing distance to all three environments and demonstrated the utility of derived categorisations. These categories may be broadly applicable in future research where the assumed underlying mechanism between residential distance to a blue space and a health outcome is direct recreational contact.info:eu-repo/semantics/publishedVersio

The adaptive evolution of herbivory in freshwater systems

Herbivory is thought to be nutritionally inefficient relative to carnivory and omnivory, but herbivory evolved from carnivory in many terrestrial and aquatic lineages, suggesting that there are advantages of eating plants. Herbivory has been well-studied in both terrestrial and aquatic systems, and there is abundant information on feedbacks between herbivores and plants, coevolution of plant and herbivore defenses, mechanisms for mediating nutrient limitation, effects of nutrient limitation on herbivore life history, and, more recently, the origins of the herbivorous diet. Researchers have sufficiently defined the ecological context and evolutionary origins of the herbivorous diet, and these main areas of research have laid the groundwork for studying herbivory as an adaptation. However, we have yet to synthesize this information in a way that allows us to establish a framework of testable adaptive hypotheses. To understand the adaptive significance of this diet transition, we review the current literature and use evidence from these works as support for five hypotheses on the evolution of herbivory from carnivory: (1) intake efficiency—herbivores use part of their food source as habitat, thus minimizing the energy/time spent searching for food and avoiding predators; (2) suboptimal habitat—herbivory allows organisms to invade and establish populations in habitats that have high primary production but low abundance of animal prey; (3) heterotroph facilitation—herbivory is adaptive because herbivores consume microbes associated with producers; (4) lipid allocation—herbivory is adaptive because producers are rich in fatty acids, which fuel reproduction and storage; and (5) disease avoidance—herbivory minimizes animal-facilitated disease transmission. Due to the extensive literature, we have limited this review to discussing herbivory in freshwater systems. To our knowledge, no prior work has compiled a comprehensive list of conditions that favor an herbivorous diet in nature. With backgrounds in both theoretical and experimental ecology, the incorporation of these hypotheses to the current literature will provide information about diet evolution, where it is currently lacking

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018

Spatial structure of the 8200 cal yr BP event in northern Europe

A synthesis of well-dated high-resolution pollen records suggests a spatial structure in the 8200 cal yr BP event in northern Europe. The temperate, thermophilous tree taxa, especially Corylus, Ulmus, and Alnus, decline abruptly between 8300 and 8000 cal yr BP at most sites located south of 61° N, whereas there is no clear change in pollen values at the sites located in the North-European tree-line region. Pollen-based quantitative temperature reconstructions and several other, independent palaeoclimate proxies, such as lacustrine oxygen-isotope records, reflect the same pattern, with no detectable cooling in the sub-arctic region. The observed patterns challenges the general view of the wide-spread occurrence of the 8200 cal yr BP event in the North Atlantic region. An alternative explanation is that the cooling during the 8200 cal yr BP event took place mostly during the winter and spring, and the ecosystems in the south responded sensitively to the cooling during the onset of the growing season. In contrast, in the sub-arctic area, where the vegetation was still dormant and lakes ice-covered, the cold event is not reflected in pollen-based or lake-sediment-based records