Showing papers by "University of North Carolina at Chapel Hill published in 2013"
Drexel University1, Yeshiva University2, Roswell Park Cancer Institute3, Virginia Commonwealth University4, Van Andel Institute5, Science Applications International Corporation6, Massachusetts Institute of Technology7, Harvard University8, University of Miami9, Icahn School of Medicine at Mount Sinai10, University of Chicago11, Howard Hughes Medical Institute12, University of Geneva13, Stanford University14, University of Oxford15, University of North Carolina at Chapel Hill16, National Institutes of Health17
TL;DR: The Genotype-Tissue Expression (GTEx) project is described, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
Abstract: Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
6,545 citations
John N. Weinstein1, John N. Weinstein2, Eric A. Collisson3, Gordon B. Mills2 +376 more•Institutions (31)
TL;DR: The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA with a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages.
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
5,294 citations
University of North Carolina at Chapel Hill1, University of Birmingham2, University of Aberdeen3, University of Barcelona4, Cleveland Clinic5, University of Cambridge6, University of Groningen7, University of Lübeck8, University of Oxford9, University of Paris10, Mayo Clinic11, University of Pennsylvania12, Boston University13, Hacettepe University14, Imperial College London15, Statens Serum Institut16, Medical University of Vienna17, Norwich University18, Harvard University19, Toho University20, University of East Anglia21
TL;DR: 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides J. Watts; Arthritis & Rheumatism
Abstract: 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides J. Jennette;R. Falk;P. Bacon;N. Basu;M. Cid;F. Ferrario;L. Flores-Suarez;W. Gross;L. Guillevin;E. Hagen;G. Hoffman;D. Jayne;C. Kallenberg;P. Lamprecht;C. Langford;R. Luqmani;A. Mahr;E. Matteson;P. Merkel;S. Ozen;C. Pusey;N. Rasmussen;A. Rees;D. Scott;U. Specks;J. Stone;K. Takahashi;R. Watts; Arthritis & Rheumatism
4,249 citations
Washington University in St. Louis1, Brown University2, University of British Columbia3, University of North Carolina at Chapel Hill4, University of Southern California5, Massachusetts Institute of Technology6, Seattle Cancer Care Alliance7, Johns Hopkins University8, University of Texas MD Anderson Cancer Center9, Nationwide Children's Hospital10, National Institutes of Health11, SRA International12, Temple University13, University of Chicago14, University of Pennsylvania15
TL;DR: It is found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients and the databases from this study are widely available to serve as a foundation for further investigations of AMl pathogenesis, classification, and risk stratification.
Abstract: BACKGROUND—Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined The relationships between patterns of mutations and epigenetic phenotypes are not yet clear METHODS—We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis RESULTS—AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes Of these, an average of 5 are in genes that are recurrently mutated in AML A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcriptionfactor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumorsuppressor genes (16%), DNA-methylation–related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%) Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories CONCLUSIONS—We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification (Funded by the National Institutes of Health) The molecular pathogenesis of acute myeloid leukemia (AML) has been studied with the use of cytogenetic analysis for more than three decades Recurrent chromosomal structural variations are well established as diagnostic and prognostic markers, suggesting that acquired genetic abnormalities (ie, somatic mutations) have an essential role in pathogenesis 1,2 However, nearly 50% of AML samples have a normal karyotype, and many of these genomes lack structural abnormalities, even when assessed with high-density comparative genomic hybridization or single-nucleotide polymorphism (SNP) arrays 3-5 (see Glossary) Targeted sequencing has identified recurrent mutations in FLT3, NPM1, KIT, CEBPA, and TET2 6-8 Massively parallel sequencing enabled the discovery of recurrent mutations in DNMT3A 9,10 and IDH1 11 Recent studies have shown that many patients with
3,980 citations
TL;DR: In this paper, the authors performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and-sequencing-based technologies, and classified them into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy number high.
Abstract: We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.
3,719 citations
Memorial Sloan Kettering Cancer Center1, Broad Institute2, Heidelberg University3, University of São Paulo4, University of California, Santa Cruz5, Harvard University6, Institute for Systems Biology7, University of Texas MD Anderson Cancer Center8, Case Western Reserve University9, Henry Ford Health System10, Duke University11, Emory University12, University of California, San Francisco13, Cedars-Sinai Medical Center14, St. Joseph's Hospital and Medical Center15, University of Florida16, Thomas Jefferson University17, University of Toronto18, Christiana Care Health System19, Mayo Clinic20, Penrose Hospital21, University of Southern California22, University of North Carolina at Chapel Hill23, Baylor College of Medicine24, University of British Columbia25, Oregon Health & Science University26, Washington University in St. Louis27
TL;DR: Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM.
3,593 citations
TL;DR: High-throughput sequencing of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease showed that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
Abstract: Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
3,310 citations
European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
2,831 citations
Cristen J. Willer1, Ellen M. Schmidt1, Sebanti Sengupta1, Gina M. Peloso2 +316 more•Institutions (87)
TL;DR: It is found that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index.
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
2,585 citations
Chad J. Creighton1, Margaret Morgan1, Preethi H. Gunaratne2, Preethi H. Gunaratne1 +288 more•Institutions (27)
TL;DR: Remodelling cellular metabolism constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Abstract: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
2,548 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston Medical Center3, University of Zurich4, University of Missouri–Kansas City5, University of Oslo6, International Olympic Committee7, University of Toronto8, University of Michigan9, Vanderbilt University Medical Center10, University of Washington11, University of North Carolina at Chapel Hill12, University of British Columbia13, Burke Rehabilitation Hospital14, Cornell University15, University of Ottawa16, Medical College of Wisconsin17, Monash University18, University of New South Wales19, University of Melbourne20, McMaster University21, Princeton University22, University of Medicine and Dentistry of New Jersey23
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston University3, University of Missouri–Kansas City4, International Olympic Committee5, University of Michigan6, Veterans Health Administration7, University of North Carolina at Chapel Hill8, University of British Columbia9, Medical College of Wisconsin10, University of Melbourne11, McMaster University12, Rutgers University13
TL;DR: This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004) and 3rd (Zurich 2008) International Consensus Conferences on Concussions in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.
Abstract: The new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the Background section. This document is developed primarily for use by physicians and healthcare professionals who are involved in the care of injured athletes, whether at the recreational, elite or professional level.
Partners HealthCare1, Brigham and Women's Hospital2, University of North Carolina at Chapel Hill3, University of California, Los Angeles4, University of Alabama at Birmingham5, Geisinger Health System6, Baylor College of Medicine7, University of California, San Francisco8, Stanford University9, American College of Medical Genetics10, National Institutes of Health11
TL;DR: It is recommended that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here and encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.
University of Wisconsin-Madison1, University of Hawaii2, University of Kiel3, Cornell University4, Max Planck Society5, Pasteur Institute6, Stanford University7, University of Helsinki8, University of Würzburg9, University of California, Berkeley10, University of New South Wales11, Harvard University12, California Institute of Technology13, University of Colorado Boulder14, University of Southern California15, University of North Carolina at Chapel Hill16, University of Connecticut17, Duke University18
TL;DR: Recent technological and intellectual advances that have changed thinking about five questions about how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; and how is homeostasis maintained between animals and their symbionts are highlighted.
Abstract: In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbioses, is fundamentally altering our understanding of animal biology. Specifically, we highlight recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction. As answers to these fundamental questions emerge, all biologists will be challenged to broaden their appreciation of these interactions and to include investigations of the relationships between and among bacteria and their animal partners as we seek a better understanding of the natural world.
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
TL;DR: These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections.
Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.
University of St Andrews1, University of Oldenburg2, Natural History Museum3, Naturalis4, Centre national de la recherche scientifique5, Michigan State University6, University of Lausanne7, University of Wyoming8, Queen Mary University of London9, University of Sheffield10, International Institute for Applied Systems Analysis11, University of Oslo12, University of Vienna13, University of Vermont14, University of East Anglia15, Spanish National Research Council16, University of Cambridge17, University of Konstanz18, University of Zurich19, Royal Botanic Garden Edinburgh20, Harvard University21, Autonomous University of Madrid22, Swiss Federal Institute of Aquatic Science and Technology23, Boston University24, Max Planck Society25, University of Neuchâtel26, University of North Carolina at Chapel Hill27, Lehigh University28, American Museum of Natural History29, University of Montpellier30, University of Liverpool31, Jagiellonian University32, Uppsala University33, German Primate Center34
TL;DR: A perspective on the context and evolutionary significance of hybridization during speciation is offered, highlighting issues of current interest and debate and suggesting that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation.
Abstract: Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.
TL;DR: This paper addresses the problem of learning similarity-preserving binary codes for efficient similarity search in large-scale image collections by proposing a simple and efficient alternating minimization algorithm, dubbed iterative quantization (ITQ), and demonstrating an application of ITQ to learning binary attributes or "classemes" on the ImageNet data set.
Abstract: This paper addresses the problem of learning similarity-preserving binary codes for efficient similarity search in large-scale image collections. We formulate this problem in terms of finding a rotation of zero-centered data so as to minimize the quantization error of mapping this data to the vertices of a zero-centered binary hypercube, and propose a simple and efficient alternating minimization algorithm to accomplish this task. This algorithm, dubbed iterative quantization (ITQ), has connections to multiclass spectral clustering and to the orthogonal Procrustes problem, and it can be used both with unsupervised data embeddings such as PCA and supervised embeddings such as canonical correlation analysis (CCA). The resulting binary codes significantly outperform several other state-of-the-art methods. We also show that further performance improvements can result from transforming the data with a nonlinear kernel mapping prior to PCA or CCA. Finally, we demonstrate an application of ITQ to learning binary attributes or "classemes" on the ImageNet data set.
Alternatives1, John Innes Centre2, University of Bonn3, University of North Carolina at Chapel Hill4, University of Wisconsin-Madison5, University of Utah6, University of Southern California7, University of Edinburgh8, University of Warwick9, Harvard University10, University College Cork11, University of Queensland12, University of Hertfordshire13, University of Potsdam14, University of California, San Diego15, Goethe University Frankfurt16, University of California, San Francisco17, University of Delaware18, Uppsala University19, Medical University of Vienna20, J. Craig Venter Institute21, University of Hawaii at Manoa22, Leibniz Association23, University of Iowa24, University of Aberdeen25, Georgia Institute of Technology26, University of California, Berkeley27, University of Groningen28, Princeton University29, University of Marburg30, University of Illinois at Urbana–Champaign31, Saarland University32, Norwegian University of Life Sciences33, Massey University34, Toyama Prefectural University35, ETH Zurich36, University of Saskatchewan37, Rutgers University38, Scripps Research Institute39, University of Helsinki40, Texas A&M University41, National Institutes of Health42, Technical University of Berlin43, University of Otago44, University of Cambridge45, University of Alberta46, Michigan State University47, Hofstra University48
TL;DR: This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products.
Commonwealth Scientific and Industrial Research Organisation1, University of Queensland2, Museum für Naturkunde3, University of Erlangen-Nuremberg4, University of the Sunshine Coast5, Nelson Mandela Metropolitan University6, Edith Cowan University7, Aberystwyth University8, Technical University of Denmark9, University of North Carolina at Chapel Hill10, University of Western Australia11, Spanish National Research Council12, University of California, Santa Barbara13, University of British Columbia14, University of Texas at Austin15, University of Plymouth16, National Marine Fisheries Service17
TL;DR: This article synthesized all available studies of the consistency of marine ecological observations with expectations under climate change This yielded a meta-database of 1,735 marine biological responses for which either regional or global climate change was considered as a driver.
Abstract: Research that combines all available studies of biological responses to regional and global climate change shows that 81–83% of all observations were consistent with the expected impacts of climate change These findings were replicated across taxa and oceanic basins Past meta-analyses of the response of marine organisms to climate change have examined a limited range of locations1,2, taxonomic groups2,3,4 and/or biological responses5,6 This has precluded a robust overview of the effect of climate change in the global ocean Here, we synthesized all available studies of the consistency of marine ecological observations with expectations under climate change This yielded a meta-database of 1,735 marine biological responses for which either regional or global climate change was considered as a driver Included were instances of marine taxa responding as expected, in a manner inconsistent with expectations, and taxa demonstrating no response From this database, 81–83% of all observations for distribution, phenology, community composition, abundance, demography and calcification across taxa and ocean basins were consistent with the expected impacts of climate change Of the species responding to climate change, rates of distribution shifts were, on average, consistent with those required to track ocean surface temperature changes Conversely, we did not find a relationship between regional shifts in spring phenology and the seasonality of temperature Rates of observed shifts in species’ distributions and phenology are comparable to, or greater, than those for terrestrial systems
TL;DR: Treatment of patients with CDI should be stratified depending on whether they have mild-to-moderate, severe, or complicated disease, and a classification of disease severity is proposed to guide therapy that is useful for clinicians.
TL;DR: The results of this study should facilitate expanded studies to identify robust heritable plant–microbe interactions at the level of individual polymorphisms by genome wide association, so that plant-microbiome interactions can ultimately be incorporated into plant breeding.
Abstract: The rhizosphere is a critical interface supporting the exchange of resources between plants and their associated soil environment. Rhizosphere microbial diversity is influenced by the physical and chemical properties of the rhizosphere, some of which are determined by the genetics of the host plant. However, within a plant species, the impact of genetic variation on the composition of the microbiota is poorly understood. Here, we characterized the rhizosphere bacterial diversity of 27 modern maize inbreds possessing exceptional genetic diversity grown under field conditions. Randomized and replicated plots of the inbreds were planted in five field environments in three states, each with unique soils and management conditions. Using pyrosequencing of bacterial 16S rRNA genes, we observed substantial variation in bacterial richness, diversity, and relative abundances of taxa between bulk soil and the maize rhizosphere, as well as between fields. The rhizospheres from maize inbreds exhibited both a small but significant proportion of heritable variation in total bacterial diversity across fields, and substantially more heritable variation between replicates of the inbreds within each field. The results of this study should facilitate expanded studies to identify robust heritable plant–microbe interactions at the level of individual polymorphisms by genome wide association, so that plant-microbiome interactions can ultimately be incorporated into plant breeding.
Broad Institute1, Harvard University2, University of North Carolina at Chapel Hill3, Karolinska Institutet4, Oslo University Hospital5, Icahn School of Medicine at Mount Sinai6, University of Queensland7, deCODE genetics8, Lundbeck9, Aarhus University Hospital10, Aarhus University11, Trinity College, Dublin12, Cardiff University13, Radboud University Nijmegen14, VU University Amsterdam15, Russian Academy16, Statens Serum Institut17, Virginia Commonwealth University18, King's College London19, Queen's University Belfast20, University of Belgrade21, Erasmus University Rotterdam22, Ludwig Maximilian University of Munich23, Martin Luther University of Halle-Wittenberg24, University of Iceland25, Tbilisi State Medical University26, National Institutes of Health27, University of Verona28, University College London29
TL;DR: The authors conducted a multi-stage genome-wide association study (GWAS) for schizophrenia and found that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia.
Abstract: Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
TL;DR: A combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations is used to obtain new information about the contribution of AEC2s to alveolar maintenance and repair.
Abstract: Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing "alveolospheres," which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα⁺ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung.
TL;DR: An evidence-based, best practises summary to assist physicians with the evaluation and management of sports concussion and how to identify knowledge gaps and areas requiring additional research is provided.
Abstract: Purpose of the statement ▸ To provide an evidence-based, best practises summary to assist physicians with the evaluation and management of sports concussion. ▸ To establish the level of evidence, knowledge gaps and areas requiring additional research. Importance of an AMSSM statement ▸ Sports medicine physicians are frequently involved in the care of patients with sports concussion. ▸ Sports medicine physicians are specifically trained to provide care along the continuum of sports concussion from the acute injury to return-to-play (RTP) decisions. ▸ The care of athletes with sports concussion is ideally performed by healthcare professionals with specific training and experience in the assessment and management of concussion. Competence should be determined by training and experience, not dictated by
University of British Columbia1, Simon Fraser University2, Johns Hopkins University3, Centers for Disease Control and Prevention4, University of Calgary5, Yale University6, McGill University7, Oregon Health & Science University8, University of California, San Francisco9, University of North Carolina at Chapel Hill10, Vanderbilt University11, Kaiser Permanente12, Harvard University13, University of Washington14, National Institutes of Health15
TL;DR: A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population.
Abstract: Background: Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.
TL;DR: In this article, the applicability and feasibility of various controls and management approaches for natural waters and drinking water supplies are discussed, and a key underlying approach that should be considered in almost all instances is nutrient (both N and P) input reductions; which have been shown to effectively reduce cyanobacterial biomass, and therefore limit health risks and frequencies of hypoxic events.
Abstract: Cyanobacteria are the Earth’s oldest oxygenic photoautotrophs and have had major impacts on shaping its biosphere. Their long evolutionary history (∼3.5 by) has enabled them to adapt to geochemical and climatic changes, and more recently anthropogenic modifications of aquatic environments, including nutrient over-enrichment (eutrophication), water diversions, withdrawals, and salinization. Many cyanobacterial genera exhibit optimal growth rates and bloom potentials at relatively high water temperatures; hence global warming plays a key role in their expansion and persistence. Bloom-forming cyanobacterial taxa can be harmful from environmental, organismal, and human health perspectives by outcompeting beneficial phytoplankton, depleting oxygen upon bloom senescence, and producing a variety of toxic secondary metabolites (e.g., cyanotoxins). How environmental factors impact cyanotoxin production is the subject of ongoing research, but nutrient (N, P and trace metals) supply rates, light, temperature, oxidative stressors, interactions with other biota (bacteria, viruses and animal grazers), and most likely, the combined effects of these factors are all involved. Accordingly, strategies aimed at controlling and mitigating harmful blooms have focused on manipulating these dynamic factors. The applicability and feasibility of various controls and management approaches is discussed for natural waters and drinking water supplies. Strategies based on physical, chemical, and biological manipulations of specific factors show promise; however, a key underlying approach that should be considered in almost all instances is nutrient (both N and P) input reductions; which have been shown to effectively reduce cyanobacterial biomass, and therefore limit health risks and frequencies of hypoxic events.
Mayo Clinic1, University of Texas MD Anderson Cancer Center2, University of Pittsburgh3, University of Wisconsin-Madison4, Columbia University5, University of Texas Southwestern Medical Center6, Indiana University7, Carolinas Medical Center8, University of Washington9, University of North Carolina at Chapel Hill10, Allegheny General Hospital11, American College of Surgeons Oncology Group12, Rutgers University13
TL;DR: The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies as mentioned in this paper.
Abstract: IMPORTANCE Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies.
TL;DR: It is proposed here that the main driving force now shaping the global food system is transnational food manufacturing, retailing and fast food service corporations whose businesses are based on very profitable, heavily promoted ultra‐processed products, many in snack form.
Abstract: The relationship between the global food system and the worldwide rapid increase of obesity and related diseases is not yet well understood. A reason is that the full impact of industrialized food processing on dietary patterns, including the environments of eating and drinking, remains overlooked and underestimated. Many forms of food processing are beneficial. But what is identified and defined here as ultra-processing, a type of process that has become increasingly dominant, at first in high-income countries, and now in middle-income countries, creates attractive, hyper-palatable, cheap, ready-to-consume food products that are characteristically energy-dense, fatty, sugary or salty and generally obesogenic. In this study, the scale of change in purchase and sales of ultra-processed products is examined and the context and implications are discussed. Data come from 79 high- and middle-income countries, with special attention to Canada and Brazil. Results show that ultra-processed products dominate the food supplies of high-income countries, and that their consumption is now rapidly increasing in middle-income countries. It is proposed here that the main driving force now shaping the global food system is transnational food manufacturing, retailing and fast food service corporations whose businesses are based on very profitable, heavily promoted ultra-processed products, many in snack form.
Utrecht University1, Loyola University Medical Center2, University of North Carolina at Chapel Hill3, University of Bonn4, Autonomous University of Madrid5, Erasmus University Rotterdam6, Health Protection Agency7, Leiden University Medical Center8, University of Iowa9, University of Hong Kong10, Ain Shams University11, University of Giessen12
TL;DR: During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus was isolated from the sputum of a patient with acute pneumonia and renal failure and was provisionally called human coronav virus Erasmus Medical Center (EMC).
Abstract: During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus (CoV) was isolated from the sputum of a patient with acute pneumonia and renal failure ([1][1], [2][2]). The isolate was provisionally called human coronavirus Erasmus Medical Center (EMC) ([3][3]). Shortly thereafter