Showing papers by "University of Turku published in 2015"
University of Zurich1, Hannover Medical School2, University of California, Davis3, Heidelberg University4, Ludwig Maximilian University of Munich5, Charité6, University of Kentucky7, University of Cologne8, Saarland University9, University of Duisburg-Essen10, University of Göttingen11, University of Hamburg12, University of Ulm13, Technische Universität München14, Otto-von-Guericke University Magdeburg15, John Radcliffe Hospital16, Winterthur Museum, Garden and Library17, University of Turku18, Gdańsk Medical University19, University of Warmia and Mazury in Olsztyn20, Medical University of Warsaw21, University of Cambridge22, University of Basel23, Catholic University of the Sacred Heart24, Innsbruck Medical University25, University of Greifswald26, Leiden University27, University of Glasgow28
TL;DR: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome and physical triggers, acute neurologics or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications.
Abstract: BackgroundThe natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. MethodsThe International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. ResultsOf 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were ...
1,721 citations
Dresden University of Technology1, Catholic University of Portugal2, Centre national de la recherche scientifique3, University of Cyprus4, Agricultural Research Organization, Volcani Center5, Maynooth University6, Swiss Federal Institute of Aquatic Science and Technology7, Norwegian University of Life Sciences8, University of Lorraine9, Vienna University of Technology10, University of Turku11, University of Catania12, Karlsruhe Institute of Technology13, University of Tartu14, Cajal Institute15, Spanish National Research Council16
TL;DR: The main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment are discussed.
Abstract: Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.
1,495 citations
TL;DR: A much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, can be much better translated to human health.
Abstract: The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.
1,423 citations
Broad Institute1, Harvard University2, University of Helsinki3, Aalto University4, Steno Diabetes Center5, VTT Technical Research Centre of Finland6, Jorvi Hospital7, University of Tartu8, University Medical Center Groningen9, University of Eastern Finland10, University of Turku11, National Institutes of Health12, RMIT University13
TL;DR: Trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T2D progressors from nonprogressors are identified.
872 citations
TL;DR: This work proposes the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard, to facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters.
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
633 citations
Thomas W. Winkler1, Anne E. Justice2, Mariaelisa Graff2, Llilda Barata3 +435 more•Institutions (106)
TL;DR: In this paper, the authors performed meta-analyses of 114 studies with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
584 citations
TL;DR: Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications, despite the prespecified noninferiority margin.
Abstract: Importance An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. Objective To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). Design, Setting, and Participants The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Interventions Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. Main Outcomes and Measures The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. Results There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of −27.0% (95% CI, −31.6% to ∞) ( P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. Conclusions and Relevance Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. Trial Registration clinicaltrials.gov Identifier:NCT01022567
555 citations
National Institutes of Health1, University of Eastern Finland2, University of London3, University College London4, University of Oulu5, University of Turku6, University of Helsinki7, University of Tampere8, University of Bristol9, University of Glasgow10, Hannover Medical School11, Technische Universität München12, Vanderbilt University13, Wellcome Trust Sanger Institute14, Turku University Hospital15, Harvard University16
TL;DR: The value of high-throughput metabolomics for biomarker discovery and improved risk assessment is substantiated and the value of net reclassification was particularly improved for persons in the 5% to 10% risk range.
Abstract: Background—High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. Methods and Results—We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women’s Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% con...
524 citations
University College London1, University of Helsinki2, Finnish Institute of Occupational Health3, French Institute of Health and Medical Research4, Karolinska Institutet5, RMIT University6, Stockholm University7, Stockholm County Council8, Federal Institute for Occupational Safety and Health9, Université libre de Bruxelles10, Ghent University11, University of Düsseldorf12, University of Duisburg-Essen13, Mid Sweden University14, Umeå University15, University of Copenhagen16, University of Turku17, University of Skövde18, Turku University Hospital19, Uppsala University20, Queen's University Belfast21, University of Essex22, University of Edinburgh23, University of Bristol24
TL;DR: Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker; these findings suggest that more attention should be paid to the management of vascular risk factors in individuals whoWork long hours.
497 citations
European Southern Observatory1, Liverpool John Moores University2, University of Western Australia3, University of St Andrews4, Max Planck Society5, Ames Research Center6, Australian Astronomical Observatory7, University of the Western Cape8, Durham University9, University of Sussex10, University of Melbourne11, University of Nottingham12, University of Sydney13, Monash University, Clayton campus14, University of Queensland15, University of Edinburgh16, University of Central Lancashire17, Australian National University18, University of Turku19, University of Canterbury20, University of Hertfordshire21, University of Oxford22, Leiden University23, Institute of Cosmology and Gravitation, University of Portsmouth24, National Institute of Astrophysics, Optics and Electronics25, Macquarie University26, National Autonomous University of Mexico27, Carnegie Institution for Science28, University of Bristol29, University of Hull30, Romanian Academy31, Queen Mary University of London32, University of Innsbruck33
TL;DR: The Galaxy And Mass Assembly (GAMA) survey as mentioned in this paper is one of the largest contemporary spectroscopic surveys of low redshift galaxies, covering an area of ∼286 deg2 (split among five survey regions) down to a limiting magnitude of r < 19.8 mag, and collecting spectra and reliable redshifts for 238'000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope.
Abstract: The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of low redshift galaxies. Covering an area of ∼286 deg2 (split among five survey regions) down to a limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238 000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm–1 m. Here, we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release of GAMA data. In this release, we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component Sersic fits, stellar masses, Hα-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72 225 objects in total). The data base serving these data is available at http://www.gama-survey.org/.
494 citations
TL;DR: This work identifies a large effect locus controlling age at maturity in Atlantic salmon, an important fitness trait in which selection favours earlier maturation in males than females, and shows it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations.
Abstract: Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict. Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict. Yet, despite intense theoretical and empirical interest, the specific loci underlying sexually antagonistic phenotypes have rarely been identified, limiting our understanding of how sexual conflict impacts genome evolution and the maintenance of genetic diversity. Here we identify a large effect locus controlling age at maturity in Atlantic salmon (Salmo salar), an important fitness trait in which selection favours earlier maturation in males than females, and show it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations. Using high-density single nucleotide polymorphism data across 57 wild populations and whole genome re-sequencing, we find that the vestigial-like family member 3 gene (VGLL3) exhibits sex-dependent dominance in salmon, promoting earlier and later maturation in males and females, respectively. VGLL3, an adiposity regulator associated with size and age at maturity in humans, explained 39% of phenotypic variation, an unexpectedly large proportion for what is usually considered a highly polygenic trait. Such large effects are predicted under balancing selection from either sexually antagonistic or spatially varying selection. Our results provide the first empirical example of dominance reversal allowing greater optimization of phenotypes within each sex, contributing to the resolution of sexual conflict in a major and widespread evolutionary trade-off between age and size at maturity. They also provide key empirical evidence for how variation in reproductive strategies can be maintained over large geographical scales. We anticipate these findings will have a substantial impact on population management in a range of harvested species where trends towards earlier maturation have been observed.
TL;DR: The detailed variation with rigidity of the helium flux spectral index is presented for the first time and the spectral index progressively hardens at rigidities larger than 100 GV.
Abstract: Knowledge of the precise rigidity dependence of the helium flux is important in understanding the
origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary
cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented
and compared to the proton flux. The detailed variation with rigidity of the helium flux spectral index is
presented for the first time. The spectral index progressively hardens at rigidities larger than 100 GV. The
rigidity dependence of the helium flux spectral index is similar to that of the proton spectral index though
the magnitudes are different. Remarkably, the spectral index of the proton to helium flux ratio increases
with rigidity up to 45 GV and then becomes constant; the flux ratio above 45 GV is well described by a
single power law.
TL;DR: A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability.
Abstract: This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health.
Uppsala University1, University of Porto2, Cardiff University3, Katholieke Universiteit Leuven4, University of Groningen5, ETH Zurich6, University of Guelph7, Stockholm University8, Durham University9, University of British Columbia10, University of Tübingen11, Aalborg University12, University of Zurich13, Colorado State University14, Swedish University of Agricultural Sciences15, Karlstad University16, Radboud University Nijmegen17, University of Warsaw18, University of Turku19, University of Hawaii at Manoa20, Instituto Gulbenkian de Ciência21, University of Graz22, United States Department of Agriculture23, University of Freiburg24, University of Eastern Finland25, Wageningen University and Research Centre26, Spanish National Research Council27, Jagiellonian University28
TL;DR: Before the real-world conservation potential of genomic research can be realized, current infrastructures need to be modified, methods must mature, analytical pipelines need to been developed, and successful case studies must be disseminated to practitioners.
Abstract: The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
TL;DR: In this article, the authors provided evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection, derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples.
TL;DR: The results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier.
Abstract: Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.
University of California, Berkeley1, University of Missouri2, University of Arizona3, Max Planck Society4, University of Stirling5, University of Turku6, Leibniz Association7, University of Cologne8, McGill University9, Pennsylvania State University10, California State University, Fullerton11, Wageningen University and Research Centre12, University of Western Australia13, University of Alberta14, University of Toronto15, Stockholm University16
TL;DR: The coevolutionary interactions between plants and butterflies are examined, and evidence for an escalating evolutionary arms-race is uncovered, providing an important connection between the origins of biodiversity, coev evolution, and the role of gene and genome duplications as a substrate for novel traits.
Abstract: Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.
TL;DR: This review discusses recent advances demonstrating that filopodia are involved in substrate tethering and environment sensing in vivo and the emerging role offilopodial proteins in tumor dissemination as mounting in vitro and in vivo.
TL;DR: In this article, a review of public participation GIS and participatory GIS (PGIS) approaches for ecosystem services to identify current and best practice has been conducted to evaluate the methods to identify best practice.
Abstract: We review public participation GIS (PPGIS) and participatory GIS (PGIS) approaches for ecosystem services to identify current and best practice. PPGIS/PGIS are spatially explicit methods that have evolved over the past decade to identify a range of ecosystem services. Although PPGIS/PGIS methods demonstrate high potential for the identification of ecosystem services, especially cultural services, there has been no review to evaluate the methods to identify best practice. Through examination of peer-reviewed, empirical PPGIS/PGIS studies, we describe the types of ecosystem services mapped, the spatial mapping methods, the sampling approaches and range of participants, the types of spatial analyses performed, and the methodological trade-offs associated with each PPGIS/PGIS mapping approach. We found that multiple methods were implemented in nearly 30 case studies worldwide with the mapping of cultural and provisioning services being most common. There was little evidence that mapped ecosystem data was used for actual decision support in land use planning. Best practice has yet to coalesce in this field that has been dominated by methodological pluralism and case study research. We suggest greater use of experimental design and long-term case studies where the influence of mapped ecosystem services on land use decisions can be assessed.
TL;DR: This consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses into the influence of the cerebellum on sensory perception.
Abstract: Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.
University of South Florida1, University of Florida2, University of Turku3, University of Eastern Finland4, Lund University5, Pacific Northwest Diabetes Research Institute6, University of Colorado Boulder7, Georgia Regents University8, Turku University Hospital9, Technische Universität München10, National Institutes of Health11, Dresden University of Technology12
TL;DR: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype, but GADA only increased until the second year and remained relatively constant.
Abstract: Aims/hypothesis
Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both.
TL;DR: In this paper, a conceptualization is developed for service experience co-creation, and multiple dimensions of the concept are identified, in terms of understanding experiential value creation and foundational sociality in contemporary markets.
Abstract: Purpose – The collective, interactive aspects of service experience are increasingly evident in contemporary research and practice, but no integrative analysis of this phenomenon has been conducted until now. The purpose of this paper is to conceptualize service experience co-creation and examines its implications for research and practice. Design/methodology/approach – To map the multi-approach research area of service experience co-creation, the study draws on literature in the fields of service management, service-dominant logic and service logic, consumer culture theory, and service innovation and design, together with invited commentaries by prominent scholars. Findings – A conceptualization is developed for “service experience co-creation,” and multiple dimensions of the concept are identified. It is postulated that service experience co-creation has wider marketing implications, in terms of understanding experiential value creation and foundational sociality in contemporary markets, as well as in t...
VU University Amsterdam1, University of Twente2, QIMR Berghofer Medical Research Institute3, University of Minnesota4, University of Edinburgh5, Radboud University Nijmegen6, University of Illinois at Urbana–Champaign7, University of Tartu8, Erasmus University Rotterdam9, University of Chicago10, Martin Luther University of Halle-Wittenberg11, University of Helsinki12, Virginia Commonwealth University13, National Research Council14, National Institutes of Health15, University of Greifswald16, Karolinska Institutet17, University of Michigan18, Washington University in St. Louis19, Estonian Academy of Sciences20, Duke University21, University of Bristol22, Princeton University23, University of Queensland24, National Institute for Health and Welfare25, University of Brescia26, Western General Hospital27, Wellcome Trust Sanger Institute28, University of Split29, University of Turku30, Indiana University31, University of Missouri32, Florida State University33, Trinity College, Dublin34, University of Southern Denmark35
TL;DR: This study identifies a novel locus for neuroticism located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies and shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants.
Abstract: Importance Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases).
Objectives To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.
Design, Setting, and Participants Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.
Main Outcomes and Measures Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.
Results A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10−9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10−8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10−12 < P < .05) and MDD (4.02 × 10−9 < P < .05) in the 2 other cohorts.
Conclusions and Relevance This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism
TL;DR: The trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry finds genetic variants at 12 new loci to be associated with blood pressure, providing new evidence for the role of DNA methylation in blood pressure regulation.
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
Queen's University Belfast1, Las Cumbres Observatory Global Telescope Network2, University of California, Santa Barbara3, University of Cambridge4, University of Southampton5, Weizmann Institute of Science6, Max Planck Society7, European Southern Observatory8, Liverpool John Moores University9, Pierre-and-Marie-Curie University10, Yale University11, Sapienza University of Rome12, Pontifical Catholic University of Chile13, Millennium Institute14, Space Science Institute15, Andrés Bello National University16, Australian National University17, Carnegie Institution for Science18, Aarhus University19, University of Chile20, Institut d'Astrophysique de Paris21, Spanish National Research Council22, University of Bonn23, Humboldt University of Berlin24, University of Würzburg25, University of Turku26, Stockholm University27, University of Copenhagen28, University of Warwick29, University of Oxford30, Lawrence Berkeley National Laboratory31, University of California, Berkeley32, University of Padua33, University of Warsaw34
TL;DR: The first data release (SSDR1) contains flux calibrated spectra from the first year (April 2012-2013), and a total of 221 confirmed supernovae were classified, and they released calibrated optical spectra and classifications publicly within 24 h of the data being taken as mentioned in this paper.
Abstract: Context. The Public European Southern Observatory Spectroscopic Survey of Transient Objects (PESSTO) began as a public spectroscopic survey in April 2012. PESSTO classifies transients from publicly available sources and wide-field surveys, and selects science targets for detailed spectroscopic and photometric follow-up. PESSTO runs for nine months of the year, January - April and August - December inclusive, and typically has allocations of 10 nights per month. Aims. We describe the data reduction strategy and data products that are publicly available through the ESO archive as the Spectroscopic Survey data release 1 (SSDR1). Methods. PESSTO uses the New Technology Telescope with the instruments EFOSC2 and SOFI to provide optical and NIR spectroscopy and imaging. We target supernovae and optical transients brighter than 20.5(m) for classification. Science targets are selected for follow-up based on the PESSTO science goal of extending knowledge of the extremes of the supernova population. We use standard EFOSC2 set-ups providing spectra with resolutions of 13-18 angstrom between 3345-9995 angstrom. A subset of the brighter science targets are selected for SOFI spectroscopy with the blue and red grisms (0.935-2.53 mu m and resolutions 23-33 angstrom) and imaging with broadband JHK(s) filters. Results. This first data release (SSDR1) contains flux calibrated spectra from the first year (April 2012-2013). A total of 221 confirmed supernovae were classified, and we released calibrated optical spectra and classifications publicly within 24 h of the data being taken (via WISeREP). The data in SSDR1 replace those released spectra. They have more reliable and quantifiable flux calibrations, correction for telluric absorption, and are made available in standard ESO Phase 3 formats. We estimate the absolute accuracy of the flux calibrations for EFOSC2 across the whole survey in SSDR1 to be typically similar to 15%, although a number of spectra will have less reliable absolute flux calibration because of weather and slit losses. Acquisition images for each spectrum are available which, in principle, can allow the user to refine the absolute flux calibration. The standard NIR reduction process does not produce high accuracy absolute spectrophotometry but synthetic photometry with accompanying JHK(s) imaging can improve this. Whenever possible, reduced SOFI images are provided to allow this. Conclusions. Future data releases will focus on improving the automated flux calibration of the data products. The rapid turnaround between discovery and classification and access to reliable pipeline processed data products has allowed early science papers in the first few months of the survey.
TL;DR: It is argued that a network pharmacology approach would enable an effective mapping of the yet unexplored target space of natural products, hence providing a systematic means to extend the druggable space of proteins implicated in various complex diseases.
TL;DR: It is demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.
Abstract: The immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumor type. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2-macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. The role of TAMs is not fully understood in breast cancer progression. Macrophage infiltration (CD68) and activation status (HLA-DRIIα, CD163) were evaluated in a large cohort of human primary breast tumors (562 tissue microarray samples), by immunohistochemistry and scored by automated image analysis algorithms. Survival between groups was compared using the Kaplan-Meier life-table method and a Cox multivariate proportional hazards model. Macrophage education by breast cancer cells was assessed by ex vivo differentiation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of breast cancer cell conditioned media (MDA-MB231, MCF-7 or T47D cell lines) and M1 or M2 inducing cytokines (respectively IFN-γ, IL-4 and IL-10). Obtained macrophages were analyzed by flow cytometry (CD14, CD16, CD64, CD86, CD200R and CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) and zymography (matrix metalloproteinase 9, MMP-9). Clinically, we found that high numbers of CD163+ M2-macrophages were strongly associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological ductal type (p<0.001) in the studied cohort of human primary breast tumors. We demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype. Furthermore, the more aggressive mesenchymal-like cell line MDA-MB231, which secretes high levels of M-CSF, skews macrophages toward the more immunosuppressive M2c subtype. This study demonstrates that human breast cancer cells influence macrophage differentiation and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.
University of Helsinki1, National Institutes of Health2, Wellcome Trust Centre for Human Genetics3, University of Tartu4, University of Ferrara5, University Medical Center Groningen6, Amgen7, Karolinska Institutet8, Uppsala University9, VU University Amsterdam10, Erasmus University Rotterdam11, Lund University12, Leiden University Medical Center13, National Institute for Health Research14, University of Lübeck15, Medical Research Council16, Technische Universität München17, University of Tampere18, Steno Diabetes Center19, Ludwig Maximilian University of Munich20, Harvard University21, Massachusetts Institute of Technology22, European Bioinformatics Institute23, University of Leicester24, Turku University Hospital25, Uppsala University Hospital26, Erasmus University Medical Center27, University College London28, University of Turku29, University of Oxford30, University of Iceland31, Minerva Foundation Institute for Medical Research32, University of Liverpool33, Imperial College London34, Wellcome Trust Sanger Institute35
TL;DR: Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, association to lipid traits in 93 loci is identified, including 79 previously identified loci with new lead SNPs and 10 new loci, including 15 locu with a low-frequency lead SNP and 10 loco with a missense lead SNP.
Abstract: Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
TL;DR: In this paper, a critical review of the Journal of International Business Studies Decade Award-winning article offers numerous contributions to international business research, and the resultant implications and the question of when it is appropriate to use the term "born global" are discussed.
Abstract: Knight and Cavusgil’s Journal of International Business Studies Decade Award-winning article offers numerous contributions to international business research. As one example, it advances cross-disciplinary conversation about entrepreneurial internationalization. A critical review of their study reveals, however, that certain findings require reinterpretation. This commentary does so, discussing the resultant implications and the question of when it is (in)appropriate to use the term “born global”. Parts of Knight and Cavusgil are then used as a foundation to identify research questions at the level of the firm. Finally, points from Cavusgil and Knight’s retrospective are used to argue that we need greater understanding of the individual(s) that are central to the firm’s internationalization behaviour. Suggestions for research are made by drawing on concepts and theory from the entrepreneurship, innovation and psychology literatures.
TL;DR: The initial concept of integrin traffic as a means to translocate adhesion receptors within the cell has now been expanded with the growing appreciation that traffic is intimately linked to the cell signalling apparatus.
Abstract: Integrins are a family of transmembrane cell surface molecules that constitute the principal adhesion receptors for the extracellular matrix (ECM) and are indispensable for the existence of multicellular organisms. In vertebrates, 24 different integrin heterodimers exist with differing substrate specificity and tissue expression. Integrin–extracellular-ligand interaction provides a physical anchor for the cell and triggers a vast array of intracellular signalling events that determine cell fate. Dynamic remodelling of adhesions, through rapid endocytic and exocytic trafficking of integrin receptors, is an important mechanism employed by cells to regulate integrin–ECM interactions, and thus cellular signalling, during processes such as cell migration, invasion and cytokinesis. The initial concept of integrin traffic as a means to translocate adhesion receptors within the cell has now been expanded with the growing appreciation that traffic is intimately linked to the cell signalling apparatus. Furthermore, endosomal pathways are emerging as crucial regulators of integrin stability and expression in cells. Thus, integrin traffic is relevant in a number of pathological conditions, especially in cancer. Nearly a decade ago we wrote a Commentary in Journal of Cell Science entitled ‘Integrin traffic’. With the advances in the field, we felt it would be appropriate to provide the growing number of researchers interested in integrin traffic with an update.