Showing papers by "Uppsala University published in 2012"
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TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.
9,282 citations
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TL;DR: A meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow identified a number of regions, including the amygdala and ventromedial prefrontal cortex, in which significant associations across studies were found.
2,174 citations
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Andrew P. Morris1, Benjamin F. Voight2, Benjamin F. Voight3, Tanya M. Teslovich4 +229 more•Institutions (53)
TL;DR: This article conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent, and identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association.
Abstract: To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
1,899 citations
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University of Kentucky1, Uppsala University2, Northwestern University3, University of Geneva4, Washington University in St. Louis5, University of Maryland, Baltimore6, Johns Hopkins University7, University of Paris8, Harvard University9, Icahn School of Medicine at Mount Sinai10, Duke University11, University of Tokyo12, Medical University of Vienna13, University of Washington14, University of Bristol15, University of British Columbia16, University of Manchester17, University of California, San Diego18, Boston University19, Rush University Medical Center20, University of Ulm21, University of Pennsylvania22, New York University23, Oregon Health & Science University24
TL;DR: Evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of A&bgr; plaques and neurofibrillary tangles.
Abstract: Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
1,589 citations
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Albert Einstein Institution1, Ewha Womans University2, University of Oxford3, Hungarian Academy of Sciences4, CERN5, University of Savoy6, Uppsala University7, Petersburg Nuclear Physics Institute8, King's College London9, Jagiellonian University10, École Normale Supérieure11, Pierre-and-Marie-Curie University12, Princeton University13, University of Copenhagen14, University of Lyon15, University of Miami16, Imperial College London17, Pennsylvania State University18, University of California, Santa Barbara19, Humboldt University of Berlin20, University of York21, Utrecht University22, Perimeter Institute for Theoretical Physics23
TL;DR: In this article, the authors present an overview of the achievements and the status of integrability in the context of the AdS/CFT correspondence as of the year 2010.
Abstract: This is the introductory chapter of a review collection on integrability in the context of the AdS/CFT correspondence. In the collection we present an overview of the achievements and the status of this subject as of the year 2010.
1,564 citations
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01 May 2012TL;DR: New data sets and their features, additional annotation tools and models provided from the website and essential interfaces and on-line services included in the OPUS project are reported.
Abstract: This paper presents the current status of OPUS, a growing language resource of parallel corpora and related tools. The focus in OPUS is to provide freely available data sets in various formats together with basic annotation to be useful for applications in computational linguistics, translation studies and cross-linguistic corpus studies. In this paper, we report about new data sets and their features, additional annotation tools and models provided from the website and essential interfaces and on-line services included in the project.
1,559 citations
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TL;DR: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
Abstract: A B S T R AC T Background Hydroxyethyl starch (HES) is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. Methods In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modi fied intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer’s acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P = 0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer’s acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer’s acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.)
1,500 citations
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TL;DR: Despite the increasing use of regional climate model (RCM) simulations in hydrological climate-change impact studies, their application is challenging due to the risk of considerable biases as discussed by the authors, which makes it difficult to apply RMC simulations to the real world.
1,393 citations
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Martin Luther University of Halle-Wittenberg1, Katholieke Universiteit Leuven2, Eppendorf (Germany)3, The Catholic University of America4, Uppsala University5, Karolinska Institutet6, Leiden University Medical Center7, Hebron University8, Radboud University Nijmegen9, Seconda Università degli Studi di Napoli10, University of São Paulo11, University of Oxford12, Medical University of Vienna13, Autonomous University of Barcelona14, Sheba Medical Center15, Ain Shams University16, Clínica Alemana17, Mount Vernon Hospital18, Bank of Cyprus19, Odense University Hospital20, University of Crete21, Marmara University22, University of Valencia23
TL;DR: This ESMO guideline is recommended to be used as the basis for treatment and management decisions, delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations.
1,299 citations
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Wageningen University and Research Centre1, University of Edinburgh2, Iowa State University3, University College London4, Agro ParisTech5, Konkuk University6, Institut national de la recherche agronomique7, Aarhus University8, Aberystwyth University9, Seoul National University10, Norwich Research Park11, Wellcome Trust Sanger Institute12, Parco Tecnologico Padano13, University of Copenhagen14, University of Illinois at Urbana–Champaign15, University of Illinois at Chicago16, Agricultural Research Service17, Kansas State University18, Uppsala University19, European Bioinformatics Institute20, United States Department of Agriculture21, Washington University in St. Louis22, University of Kent23, Science for Life Laboratory24, Gyeongsang National University25, Genetic Information Research Institute26, Durham University27, University of California, Davis28, Pennsylvania State University29, University of Minnesota30, Jeju National University31, François Rabelais University32, University of California, Berkeley33, Glasgow Caledonian University34, Leipzig University35, Huazhong Agricultural University36
TL;DR: The assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago.
Abstract: For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
1,189 citations
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TL;DR: An overview of the concepts of stability that are relevant for microbial communities is provided, and thoughts about the unique insights that systems perspectives – informed by meta-omics data – may provide about microbial community stability are concluded.
Abstract: Microbial communities are at the heart of all ecosystems, and yet microbial community behavior in disturbed environments remains difficult to measure and predict. Understanding the drivers of microbial community stability, including resistance (insensitivity to disturbance) and resilience (the rate of recovery after disturbance) is important for predicting community response to disturbance. Here, we provide an overview of the concepts of stability that are relevant for microbial communities. First, we highlight insights from ecology that are useful for defining and measuring stability. To determine whether general disturbance responses exist for microbial communities, we next examine representative studies from the literature that investigated community responses to press (long-term) and pulse (short-term) disturbances in a variety of habitats. Then we discuss the biological features of individual microorganisms, of microbial populations, and of microbial communities that may govern overall community stability. We conclude with thoughts about the unique insights that systems perspectives - informed by meta-omics data - may provide about microbial community stability.
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Karol Estrada1, Unnur Styrkarsdottir, Evangelos Evangelou2, Yi-Hsiang Hsu3 +187 more•Institutions (69)
TL;DR: Light is shed on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility and within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways.
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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TL;DR: This review outlines the current information on VEGF signal transduction in relation to blood and lymphatic vessel biology and develops treatments to halt blood vessel formation, angiogenesis in diseases that involve tissue growth and inflammation, such as cancer.
Abstract: Vascular endothelial growth factors (VEGFs) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in the adult. It is therefore important to understand the mechanism of action of this family of five mammalian ligands, which act through three receptor tyrosine kinases (RTKs). In addition, coreceptors like neuropilins (NRPs) and integrins associate with the ligand/receptor signaling complex and modulate the output. Therapeutics to block several of the VEGF signaling components have been developed with the aim to halt blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. In this review, we outline the current information on VEGF signal transduction in relation to blood and lymphatic vessel biology.
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University College London1, University of Helsinki2, Finnish Institute of Occupational Health3, University of Edinburgh4, RMIT University5, Stockholm University6, Karolinska Institutet7, Federal Institute for Occupational Safety and Health8, Université libre de Bruxelles9, Ghent University10, University of Düsseldorf11, University of Bristol12, French Institute of Health and Medical Research13, Mid Sweden University14, Queen's University Belfast15, Umeå University16, University of Copenhagen17, University of Turku18, Turku University Hospital19, Uppsala University20
TL;DR: The findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking.
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Alisa K. Manning1, Alisa K. Manning2, Alisa K. Manning3, Robert A. Scott +240 more•Institutions (69)
TL;DR: Six previously unknown loci associated with fasting insulin at P < 5 × 10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals are presented.
Abstract: Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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TL;DR: The list of potential CE catalysts, which can help reduce the cost of DSCs and thereby encourage their fundamental research and commercial application is expanded, to include carbides, nitrides and oxides.
Abstract: Three classes (carbides, nitrides and oxides) of nanoscaled early-transition-metal catalysts have been proposed to replace the expensive Pt catalyst as counter electrodes (CEs) in dye-sensitized solar cells (DSCs). Of these catalysts, Cr3C2, CrN, VC(N), VN, TiC, TiC(N), TiN, and V2O3 all showed excellent catalytic activity for the reduction of I3– to I– in the electrolyte. Further, VC embedded in mesoporous carbon (VC–MC) was prepared through in situ synthesis. The I3–/I– DSC based on the VC–MC CE reached a high power conversion efficiency (PCE) of 7.63%, comparable to the photovoltaic performance of the DSC using a Pt CE (7.50%). In addition, the carbide catalysts demonstrated catalytic activity higher than that of Pt for the regeneration of a new organic redox couple of T2/T–. The T2/T– DSCs using TiC and VC–MC CEs showed PCEs of 4.96 and 5.15%, much higher than that of the DSC using a Pt CE (3.66%). This work expands the list of potential CE catalysts, which can help reduce the cost of DSCs and thereby...
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SLAC National Accelerator Laboratory1, Max Planck Society2, Arizona State University3, Cornell University4, State University of New York System5, Johns Hopkins University Applied Physics Laboratory6, European Synchrotron Radiation Facility7, University of Gothenburg8, University of Lübeck9, University of Hamburg10, Uppsala University11
TL;DR: Serial femtosecond crystallography (SFX) is applied using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals of the well-characterized model protein lysozyme, demonstrating the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
Abstract: Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
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TL;DR: Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations and further functional analysis of these newly discovered loci will further improve the understanding of glycemic control.
Abstract: Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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TL;DR: A tight correlation between the activity of the locus coeruleus (i.e., the "hub" of the noradrenergic system) and pupillary dilation and neurophysiological findings provide new important insights to the meaning of pupillary responses for mental activity.
Abstract: The measurement of pupil diameter in psychology (in short, "pupillometry") has just celebrated 50 years. The method established itself after the appearance of three seminal studies (Hess & Polt, 1960, 1964; Kahneman & Beatty, 1966). Since then, the method has continued to play a significant role within the field, and pupillary responses have been successfully used to provide an estimate of the "intensity" of mental activity and of changes in mental states, particularly changes in the allocation of attention and the consolidation of perception. Remarkably, pupillary responses provide a continuous measure regardless of whether the participant is aware of such changes. More recently, research in neuroscience has revealed a tight correlation between the activity of the locus coeruleus (i.e., the "hub" of the noradrenergic system) and pupillary dilation. As we discuss in this short review, these neurophysiological findings provide new important insights to the meaning of pupillary responses for mental activity. Finally, given that pupillary responses can be easily measured in a noninvasive manner, occur from birth, and can occur in the absence of voluntary, conscious processes, they constitute a very promising tool for the study of preverbal (e.g., infants) or nonverbal participants (e.g., animals, neurological patients).
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Duke University1, Uppsala University2, University of Kentucky3, University of Alberta4, Katholieke Universiteit Leuven5, Auckland City Hospital6, Flinders University7, Merck & Co.8, University of Tennessee Health Science Center9, University of Perugia10, University of Freiburg11, University of Barcelona12, Ufuk University13, Henry Ford Health System14, Peking Union Medical College15, Leiden University16, Cleveland Clinic17, Pierre-and-Marie-Curie University18, University of São Paulo19, Kumamoto University20, University of Basel21, University of Chile22, University of Sheffield23, University of Ferrara24, Thomas Jefferson University25, Charles University in Prague26
TL;DR: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage.
Abstract: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
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University of Cambridge1, University of Bristol2, University of Eastern Finland3, University of Helsinki4, University of Gothenburg5, University of Lille Nord de France6, Laval University7, Harvard University8, University of Edinburgh9, University of Sheffield10, Stanford University11, Uppsala University12, University of Pennsylvania13, Karolinska Institutet14, Pierre-and-Marie-Curie University15, University of Birmingham16, University of Michigan17, Technische Universität München18, Utrecht University19, University of Amsterdam20, University of Iceland21, National Institute for Health and Welfare22, National Institutes of Health23, Imperial College London24, Copenhagen University Hospital25, University of Copenhagen26, Clinical Trial Service Unit27, National Institute for Health Research28, deCODE genetics29, University of Oxford30
TL;DR: In this article, a functional genetic variant known to affect IL6R signalling was studied to assess whether this pathway is causally relevant to coronary heart disease, and Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking.
Abstract: Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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TL;DR: This study provides a roadmap to the emerging field of speciation genomics by showing that the genomic landscape of species differentiation is highly heterogeneous with approximately 50 ‘divergence islands’ showing up to 50-fold higher sequence divergence than the genomic background.
Abstract: Unravelling the genomic landscape of divergence between lineages is key to understanding speciation. The naturally hybridizing collared flycatcher and pied flycatcher are important avian speciation models that show pre- as well as postzygotic isolation. We sequenced and assembled the 1.1-Gb flycatcher genome, physically mapped the assembly to chromosomes using a low-density linkage map and re-sequenced population samples of each species. Here we show that the genomic landscape of species differentiation is highly heterogeneous with approximately 50 'divergence islands' showing up to 50-fold higher sequence divergence than the genomic background. These non-randomly distributed islands, with between one and three regions of elevated divergence per chromosome irrespective of chromosome size, are characterized by reduced levels of nucleotide diversity, skewed allele-frequency spectra, elevated levels of linkage disequilibrium and reduced proportions of shared polymorphisms in both species, indicative of parallel episodes of selection. Proximity of divergence peaks to genomic regions resistant to sequence assembly, potentially including centromeres and telomeres, indicate that complex repeat structures may drive species divergence. A much higher background level of species divergence of the Z chromosome, and a lower proportion of shared polymorphisms, indicate that sex chromosomes and autosomes are at different stages of speciation. This study provides a roadmap to the emerging field of speciation genomics.
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TL;DR: It is concluded that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.
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TL;DR: A benchmark for force fields is devised in order to test the ability of existing force fields to reproduce some key properties of organic liquids, namely, the density, enthalpy of vaporization, the surface tension, the heat capacity at constant volume and pressure, the isothermal compressibility, the volumetric expansion coefficient, and the static dielectric constant.
Abstract: The chemical composition of small organic molecules is often very similar to amino acid side chains or the bases in nucleic acids, and hence there is no a priori reason why a molecular mechanics force field could not describe both organic liquids and biomolecules with a single parameter set. Here, we devise a benchmark for force fields in order to test the ability of existing force fields to reproduce some key properties of organic liquids, namely, the density, enthalpy of vaporization, the surface tension, the heat capacity at constant volume and pressure, the isothermal compressibility, the volumetric expansion coefficient, and the static dielectric constant. Well over 1200 experimental measurements were used for comparison to the simulations of 146 organic liquids. Novel polynomial interpolations of the dielectric constant (32 molecules), heat capacity at constant pressure (three molecules), and the isothermal compressibility (53 molecules) as a function of the temperature have been made, based on expe...
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TL;DR: An overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals.
Abstract: Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.
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TL;DR: A combined search for the Standard Model Higgs boson with the ATLAS experiment at the LHC using datasets corresponding to integrated luminosities from 1.04 fb(-1) to 4.9 fb(1) of pp collisions is described in this paper.
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J. L. Abelleira Fernandez1, J. L. Abelleira Fernandez2, C. Adolphsen3, A. Akay4 +195 more•Institutions (54)
TL;DR: The Large Hadron Electron Collider (LHeC) as discussed by the authors was designed to achieve an integrated luminosity of O(100 ),fb$^{-1}, which is the cleanest high resolution microscope of mankind.
Abstract: This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100)\,fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC.
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TL;DR: The results suggest that migration from southern Europe catalyzed the spread of agriculture and that admixture in the wake of this expansion eventually shaped the genomic landscape of modern-day Europe.
Abstract: The farming way of life originated in the Near East some 11,000 years ago and had reached most of the European continent 5000 years later. However, the impact of the agricultural revolution on demography and patterns of genomic variation in Europe remains unknown. We obtained 249 million base pairs of genomic DNA from ~5000-year-old remains of three hunter-gatherers and one farmer excavated in Scandinavia and find that the farmer is genetically most similar to extant southern Europeans, contrasting sharply to the hunter-gatherers, whose distinct genetic signature is most similar to that of extant northern Europeans. Our results suggest that migration from southern Europe catalyzed the spread of agriculture and that admixture in the wake of this expansion eventually shaped the genomic landscape of modern-day Europe.
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Goethe University Frankfurt1, Tufts University2, Erasmus University Rotterdam3, University of Tromsø4, University of Eastern Finland5, Ludwig Maximilian University of Munich6, French Institute of Health and Medical Research7, University of Milan8, University of Edinburgh9, University of Miami10, EHESP11, Columbia University12, Uppsala University13, University of Gothenburg14, Tulane University15, University of Cambridge16, Utrecht University17
TL;DR: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven and no conclusion can be derived for the use of c IMT progression as a surrogate in clinical trials.
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TL;DR: This review shows that mast cells play an active role in such diverse diseases as asthma, rhinitis, middle ear infection, and pulmonary fibrosis and may also have a central role in the initiation of the allergic immune response.