Showing papers by "Uppsala University published in 2015"
University of Chicago1, University of Padua2, McGill University3, Johns Hopkins University4, French Institute of Health and Medical Research5, Uppsala University6, University of California, San Francisco7, MedStar Washington Hospital Center8, Katholieke Universiteit Leuven9, University of Liège10, Harvard University11, Ghent University Hospital12, University of Toronto13
TL;DR: This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases.
Abstract: The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
11,568 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
TL;DR: Large-scale single-cell RNA sequencing is used to classify cells in the mouse somatosensory cortex and hippocampal CA1 region and found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex.
Abstract: The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.
2,675 citations
TL;DR: Clumpak, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology by automating the postprocessing of results of model‐based population structure analyses.
Abstract: The identification of the genetic structure of populations from multilocus genotype data has become a central component of modern population-genetic data analysis. Application of model-based clustering programs often entails a number of steps, in which the user considers different modelling assumptions, compares results across different predetermined values of the number of assumed clusters (a parameter typically denoted K), examines multiple independent runs for each fixed value of K, and distinguishes among runs belonging to substantially distinct clustering solutions. Here, we present CLUMPAK (Cluster Markov Packager Across K), a method that automates the postprocessing of results of model-based population structure analyses. For analysing multiple independent runs at a single K value, CLUMPAK identifies sets of highly similar runs, separating distinct groups of runs that represent distinct modes in the space of possible solutions. This procedure, which generates a consensus solution for each distinct mode, is performed by the use of a Markov clustering algorithm that relies on a similarity matrix between replicate runs, as computed by the software CLUMPP. Next, CLUMPAK identifies an optimal alignment of inferred clusters across different values of K, extending a similar approach implemented for a fixed K in CLUMPP and simplifying the comparison of clustering results across different K values. CLUMPAK incorporates additional features, such as implementations of methods for choosing K and comparing solutions obtained by different programs, models, or data subsets. CLUMPAK, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology.
2,252 citations
TL;DR: This article conducted a meta-analysis of coronary artery disease (CAD) cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 millions low-frequency (0.005 < MAF < 0.5) variants.
Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
1,839 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
University of Cologne1, Stanford University2, University of Ulsan3, Hanyang University4, Vancouver General Hospital5, University of Bonn6, University of North Carolina at Chapel Hill7, University of Rostock8, Epigenomics AG9, University of Tsukuba10, University Hospital Heidelberg11, Heidelberg University12, Schiller International University13, University of Zurich14, Vanderbilt University15, University of Belgrade16, Peter MacCallum Cancer Centre17, Casa Sollievo della Sofferenza18, University of Liverpool19, University of Zagreb20, Charité21, Oslo University Hospital22, VU University Medical Center23, Uppsala University24, Haukeland University Hospital25, Max Planck Society26, Memorial Sloan Kettering Cancer Center27, French Institute of Health and Medical Research28
TL;DR: This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
Abstract: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
1,504 citations
TL;DR: A genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 that encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells is reported.
Abstract: Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).
1,342 citations
University of Edinburgh1, University of Greifswald2, University of London3, Queen Mary University of London4, University of Trieste5, Vita-Salute San Raffaele University6, University of Tartu7, National Institutes of Health8, University of Oxford9, Johns Hopkins University10, Erasmus University Rotterdam11, University of Verona12, University of Iceland13, University of Otago14, Uppsala University15, University of Lübeck16, University of Split17, Harvard University18, University Hospital of Lausanne19, Ludwig Maximilian University of Munich20, University of Auckland21, VU University Amsterdam22, University of Regensburg23, Max Planck Society24, Greifswald University Hospital25, University of Helsinki26, Charles III University of Madrid27, Wellcome Trust Sanger Institute28, University College London29, Leiden University30, Catholic University of the Sacred Heart31, University of Bern32, University of Freiburg33
TL;DR: Interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, and regression-type analyses in a non BMI-stratified overall sample suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum.
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
TL;DR: The current manuscript is an update of the original Practical Guide, published in June 2013, and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence.
Abstract: The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu).
TL;DR: The mechanisms regulating the formation and maintenance of the BBB and functions of BBB-associated cell types are examined and the growing evidence associating BBB breakdown with the pathogenesis of inherited monogenic neurological disorders and complex multifactorial diseases, including Alzheimer's disease is discussed.
TL;DR: The discovery of ‘Lokiarchaeota’ is described, a novel candidate archaeal phylum which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eUKaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities.
Abstract: The origin of the eukaryotic cell remains one of the most contentious puzzles in modern biology. Recent studies have provided support for the emergence of the eukaryotic host cell from within the archaeal domain of life, but the identity and nature of the putative archaeal ancestor remain a subject of debate. Here we describe the discovery of 'Lokiarchaeota', a novel candidate archaeal phylum, which forms a monophyletic group with eukaryotes in phylogenomic analyses, and whose genomes encode an expanded repertoire of eukaryotic signature proteins that are suggestive of sophisticated membrane remodelling capabilities. Our results provide strong support for hypotheses in which the eukaryotic host evolved from a bona fide archaeon, and demonstrate that many components that underpin eukaryote-specific features were already present in that ancestor. This provided the host with a rich genomic 'starter-kit' to support the increase in the cellular and genomic complexity that is characteristic of eukaryotes.
TL;DR: Authors/Task Force Members: Silvia G. Priori (Chairperson), Carina Blomström-Lundqvist (Co-chairperson) (Sweden), Andrea Mazzanti† (Italy), Nico Blom (The Netherlands), Martin Borggrefe (Germany), John Camm (UK), Perry Mark Elliott (UK).
Abstract: 2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
TL;DR: Support is provided to the hypothesis that work-related stress defined as job strain is linked to an increased risk of AF by pointing towards a dose-response relationship when taking accumulated exposure to job strain over time into account.
Abstract: Introduction. Atrial fibrillation (AF) is a common heart rhythm disorder. Several life-style factors have been identified as risk factors for AF, but less is known about the impact of work-related stress. This study aims to evaluate the association between work-related stress, defined as job strain, and risk of AF. Methods. Data from the Swedish WOLF study was used, comprising 10,121 working men and women. Job strain was measured by the demand-control model. Information on incident AF was derived from national registers. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and AF risk. Results. In total, 253 incident AF cases were identified during a total follow-up time of 132,387 person-years. Job strain was associated with AF risk in a time-dependent manner, with stronger association after 10.7 years of follow-up (HR 1.93, 95% CI 1.10–3.36 after 10.7 years, versus HR 1.11, 95% CI 0.67–1.83 before 10.7 years). The results pointed towards a dose-response relationship when taking accumulated exposure to job strain over time into account. Conclusion. This study provides support to the hypothesis that work-related stress defined as job strain is linked to an increased risk of AF.
TL;DR: Bismuth perovskites have very promising properties for further development in solar cells and a power conversion efficiency of over 1% is obtained.
Abstract: Low-toxic bismuth-based perovskites are prepared for the possible replacement of lead perovskite in solar cells. The perovskites have a hexagonal crystalline phase and light absorption in the visible region. A power conversion efficiency of over 1% is obtained for a solar cell with Cs3 Bi2 I9 perovskite, and it is concluded that bismuth perovskites have very promising properties for further development in solar cells.
TL;DR: It is reported that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood.
Illinois State University1, York University2, California University of Pennsylvania3, Washington State University4, United States Geological Survey5, Norwegian Institute for Air Research6, University of Wisconsin-Madison7, Uppsala University8, University of Konstanz9, University at Albany, SUNY10, Leibniz Association11, University of Waikato12, University of Helsinki13, University of Minnesota14, Indian Ministry of Environment and Forests15, Colorado State University16, University of Adelaide17, Marine Institute of Memorial University of Newfoundland18, University of Innsbruck19, University of Florida20, Cornell University21, International Institute for Sustainable Development22, California Institute of Technology23, Irkutsk State University24, Estonian University of Life Sciences25, Ritsumeikan University26, Finnish Environment Institute27, Great Lakes Environmental Research Laboratory28, Swiss Federal Institute of Aquatic Science and Technology29, University of California, Santa Barbara30, University of Hamburg31, Russian Academy of Sciences32, Royal Museum for Central Africa33, National Research Council34, Ontario Ministry of the Environment35, University of New Hampshire36, University of Washington37, University of California, Davis38, Melikşah University39, University of Vienna40, National Institute of Water and Atmospheric Research41, University of Eastern Finland42, Seqwater43, Miami University44, Chinese Academy of Sciences45
TL;DR: In the first worldwide synthesis of in situ and satellite-derived lake data, this paper found that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009.
Abstract: In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
TL;DR: The whole-genome re-sequencing of 120 individuals representing all of the Darwin’s finch species and two close relatives finds extensive evidence for interspecific gene flow throughout the radiation.
Abstract: Darwin's finches, inhabiting the Galapagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-s ...
TL;DR: It is suggested that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.
TL;DR: In this article, the authors summarized existing research on PV self-consumption and options to improve it, namely energy storage and load management, also called demand side management (DSM), and showed that it is possible to increase the relative selfconsumption with a battery storage capacity of 0.5-1. kW.
TL;DR: In this article, precise and accurate parameters for late-type (late K and M) dwarf stars are important for characterization of any orbiting planets, but such determinations have been hampered by these stars' compl...
Abstract: Precise and accurate parameters for late-type (late K and M) dwarf stars are important for characterization of any orbiting planets, but such determinations have been hampered by these stars' compl ...
Australian Astronomical Observatory1, University of Sydney2, Australian National University3, University of New South Wales4, Macquarie University5, University of Ljubljana6, University of Southern Queensland7, Max Planck Society8, Monash University9, University of Cambridge10, INAF11, Joint Institute for Nuclear Astrophysics12, University of Minnesota13, University of Western Australia14, Uppsala University15, Harvard University16
TL;DR: The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectroscopic survey using the newly commissioned High Efficiency and Resolution Multi-element Spectrograph (HERMES) on the Anglo-Australian Telescope as discussed by the authors.
Abstract: The Galactic Archaeology with HERMES (GALAH) survey is a large high-resolution spectroscopic survey using the newly commissioned High Efficiency and Resolution Multi-Element Spectrograph (HERMES) on the Anglo-Australian Telescope. The HERMES spectrograph provides high-resolution (R ~ 28 000) spectra in four passbands for 392 stars simultaneously over a 2 deg field of view. The goal of the survey is to unravel the formation and evolutionary history of the Milky Way, using fossil remnants of ancient star formation events which have been disrupted and are now dispersed throughout the Galaxy. Chemical tagging seeks to identify such dispersed remnants solely from their common and unique chemical signatures; these groups are unidentifiable from their spatial, photometric or kinematic properties. To carry out chemical tagging, the GALAH survey will acquire spectra for a million stars down to V ~ 14. The HERMES spectra of FGK stars contain absorption lines from 29 elements including light proton-capture elements, α-elements, odd-Z elements, iron-peak elements and n-capture elements from the light and heavy s-process and the r-process. This paper describes the motivation and planned execution of the GALAH survey, and presents some results on the first-light performance of HERMES.
TL;DR: It is concluded that OSA is highly prevalent in the population, related to age and obesity, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA.
Abstract: The prevalence of obstructive sleep apnea (OSA) defined at an apnea-hypopnea index (AHI) ≥5 was a mean of 22% (range, 9-37%) in men and 17% (range, 4-50%) in women in eleven published epidemiological studies published between 1993 and 2013. OSA with excessive daytime sleepiness occurred in 6% (range, 3-18%) of men and in 4% (range, 1-17%) of women. The prevalence increased with time and OSA was reported in 37% of men and in 50% of women in studies from 2008 and 2013 respectively. OSA is more prevalent in men than in women and increases with age and obesity. Smoking and alcohol consumption are also suggested as risk factors, but the results are conflicting. Excessive daytime sleepiness is suggested as the most important symptom of OSA, but only a fraction of subjects with AHI >5 report daytime sleepiness and one study did not find any relationship between daytime sleepiness and sleep apnea in women. Stroke and hypertension and coronary artery disease are associated with sleep apnea. Cross-sectional studies indicate an association between OSA and diabetes mellitus. Patients younger than 70 years run an increased risk of early death if they suffer from OSA. It is concluded that OSA is highly prevalent in the population. It is related to age and obesity. Only a part of subjects with OSA in the population have symptoms of daytime sleepiness. The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design and characteristics of included subjects including effects of the obesity epidemic. Cardiovascular disease, especially stroke is related to OSA, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA.
TL;DR: The Vienna atomic line database (VALD) as discussed by the authors is a collection of critically evaluated laboratory parameters for individual atomic transitions, complemented by theoretical calculations, used by astronomers for stellar spectroscopic studies.
Abstract: Vienna atomic line database (VALD) is a collection of critically evaluated laboratory parameters for individual atomic transitions, complemented by theoretical calculations. VALD is actively used by astronomers for stellar spectroscopic studies—model atmosphere calculations, atmospheric parameter determinations, abundance analysis etc. The two first VALD releases contained parameters for atomic transitions only. In a major upgrade of VALD—VALD3, publically available from spring 2014, atomic data was complemented with parameters of molecular lines. The diatomic molecules C2, CH, CN, CO, OH, MgH, SiH, TiO are now included. For each transition VALD provides species name, wavelength, energy, quantum number J and Lande-factor of the lower and upper levels, radiative, Stark and van der Waals damping factors and a full description of electronic configurarion and term information of both levels. Compared to the previous versions we have revised and verify all of the existing data and added new measurements and calculations for transitions in the range between 20 A and 200 microns. All transitions were complemented with term designations in a consistent way and electron configurations when available. All data were checked for consistency: listed wavelength versus Ritz, selection rules etc. A new bibliographic system keeps track of literature references for each parameter in a given transition throughout the merging process so that every selected data entry can be traced to the original source. The query language and the extraction tools can now handle various units, vacuum and air wavelengths. In the upgrade process we had an intensive interaction with data producers, which was very helpful for improving the quality of the VALD content.
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.
University of Cambridge1, Utrecht University2, University of Glasgow3, University of Oslo4, Howard University5, Copenhagen University Hospital6, University of Washington7, University of Western Australia8, Medical University of South Carolina9, University of Eastern Finland10, Analytical Services11, University of Pittsburgh12, University of New South Wales13, University of California, San Diego14, Norwegian Institute of Public Health15, Portland State University16, University of Hawaii17, National Institutes of Health18, Uppsala University19, University Medical Center Groningen20, University of Gothenburg21, University of Iowa22, German Cancer Research Center23, Pasteur Institute24, Baker IDI Heart and Diabetes Institute25, Osaka University26, Istanbul University27, City College of New York28, Boston University29, University of Oxford30, University of Southampton31, Erasmus University Rotterdam32, French Institute of Health and Medical Research33, Paris Diderot University34, Harvard University35, Columbia University Medical Center36, MedStar Health37, Greifswald University Hospital38, VU University Amsterdam39, Maastricht University Medical Centre40, Istituto Superiore di Sanità41, Wageningen University and Research Centre42, University of Edinburgh43, University of London44, University of Padua45, University of Bristol46, Cardiff University47, Ludwig Maximilian University of Munich48, Leiden University Medical Center49, University of Sydney50, University College London51, Medical Research Council52, University of North Carolina at Chapel Hill53, University of Tromsø54, Lund University55, Albert Einstein College of Medicine56, Johns Hopkins University57
TL;DR: Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Johns Hopkins University1, The George Institute for Global Health2, National University of Singapore3, University of California, San Diego4, University of Alabama at Birmingham5, University of Southampton6, Dokkyo Medical University7, German Cancer Research Center8, San Francisco VA Medical Center9, University of Calgary10, Queen Elizabeth Hospital Birmingham11, Utrecht University12, University of Tsukuba13, Nagoya University14, University Medical Center Groningen15, Tufts Medical Center16, University of Oxford17, Uppsala University18, Dalarna University19
TL;DR: In this paper, a meta-analytic approach was used to assess the usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for predicting cardiovascular outcomes.
TL;DR: It is shown that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes, and RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.
Abstract: Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA–DNA triplex formation. We have found that RNA–DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.