Showing papers by "University of British Columbia published in 2013"
Wellcome Trust Sanger Institute1, Wellcome Trust2, Cambridge University Hospitals NHS Foundation Trust3, University of British Columbia4, University of Cambridge5, The Breast Cancer Research Foundation6, Oslo University Hospital7, University of Oslo8, University of Münster9, Université libre de Bruxelles10, German Cancer Research Center11, University of Iceland12, Erasmus University Rotterdam13, Paris Descartes University14, French Institute of Health and Medical Research15, University of Paris16, Broad Institute17, University of Bergen18, University of Oviedo19, University of Queensland20, University of Glasgow21, Harvard University22, United States Department of Veterans Affairs23, Netherlands Cancer Institute24, University of Kiel25, Radboud University Nijmegen26, King's College London27, Curie Institute28, Bankstown Lidcombe Hospital29, University of New South Wales30, University of Barcelona31
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
7,904 citations
University of British Columbia1, Johns Hopkins University2, Max Planck Society3, Institute for the Physics and Mathematics of the Universe4, Princeton University5, University of Toronto6, Perimeter Institute for Theoretical Physics7, University of Minnesota8, Goddard Space Flight Center9, University of Chicago10, Brown University11, University of California, Los Angeles12
TL;DR: In this paper, the authors present cosmological parameter constraints based on the final nine-year WMAP data, in conjunction with a number of additional cosmology data sets.
Abstract: We present cosmological parameter constraints based on the final nine-year WMAP data, in conjunction with a number of additional cosmological data sets. The WMAP data alone, and in combination, continue to be remarkably well fit by a six-parameter CDM model. When WMAP data are combined with measurements of the high-l cosmic microwave background (CMB) anisotropy, the baryon acoustic oscillation (BAO) scale, and the Hubble constant, the matter and energy densities, bh 2 , ch 2 , and , are each determined to a precision of 1.5%. The amplitude of the primordial spectrum is measured to within 3%, and there is now evidence for a tilt in the primordial spectrum at the 5 level, confirming the first detection of tilt based on the five-year WMAP data. At the end of the WMAP mission, the nine-year data decrease the allowable volume of the six-dimensional CDM parameter space by a factor of 68,000 relative to pre-WMAP measurements. We investigate a number of data combinations and show that their CDM parameter fits are consistent. New limits on deviations from the six-parameter model are presented, for example: the fractional contribution of tensor modes is limited to r < 0.13 (95% CL); the spatial curvature parameter is limited to k = 0.0027 +0.0039 0.0038 ; the summed mass of neutrinos is limited to P m < 0.44 eV (95% CL); and the number of relativistic species is found to lie within Ne = 3.84±0.40, when the full data are analyzed. The joint constraint on Ne and the primordial helium abundance, YHe, agrees with the prediction of standard Big Bang nucleosynthesis. We compare recent Planck measurements of the Sunyaev‐Zel’dovich eect with our seven-year measurements, and show their mutual agreement. Our analysis of the polarization pattern around temperature extrema is updated. This confirms a fundamental prediction of the standard cosmological model and provides a striking illustration of acoustic oscillations and adiabatic initial conditions in the early universe. Subject headings: cosmic microwave background, cosmology: observations, early universe, dark matter, space vehicles, space vehicles: instruments, instrumentation: detectors, telescopes
5,488 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
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
University of Edinburgh1, University of Calgary2, Medical University of Graz3, The George Institute for Global Health4, University of Cambridge5, VU University Amsterdam6, University of British Columbia7, Sunnybrook Health Sciences Centre8, German Center for Neurodegenerative Diseases9, Paris Diderot University10, University of California, Davis11, Radboud University Nijmegen Medical Centre12, Ludwig Maximilian University of Munich13, University College London14, Harvard University15, University of Western Ontario16, The Chinese University of Hong Kong17, Maastricht University18, University of Florence19, Otto-von-Guericke University Magdeburg20, Newcastle University21, National University of Singapore22, Leiden University Medical Center23, University of Saint Mary24
TL;DR: This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
Abstract: Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
3,691 citations
University of British Columbia1, East Kent Hospitals University Nhs Foundation Trust2, Newcastle University3, Johns Hopkins University4, University of Groningen5, University of York6, University of Calgary7, University of the Ryukyus8, Tufts University9, University of California, San Francisco10, Peking University11, University of Oxford12
3,645 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: Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance.
3,497 citations
Max Planck Society1, McGill University2, University of Toronto3, University of Manchester4, University of Sheffield5, German Aerospace Center6, University of Amsterdam7, ASTRON8, Lebedev Physical Institute9, University of Warwick10, West Virginia University11, University of Virginia12, National Radio Astronomy Observatory13, University of British Columbia14
TL;DR: Pulsar J0348+0432 is only the second neutron star with a precisely determined mass of 2 M☉
Abstract: Many physically motivated extensions to general relativity (GR) predict significant deviations at energies present in massive neutron stars. We report the measurement of a 2.01 \(\pm \) 0.04 solar mass (M\(_\odot \)) pulsar in a 2.46-h orbit around a 0.172 \(\pm \) 0.003 M\(_\odot \) white dwarf. The high pulsar mass and the compact orbit make this system a sensitive laboratory of a previously untested strong-field gravity regime. Thus far, the observed orbital decay agrees with GR, supporting its validity even for the extreme conditions present in the system. The resulting constraints on deviations support the use of GR-based templates for ground-based gravitational wave detection experiments. Additionally, the system strengthens recent constraints on the properties of dense matter and provides novel insight to binary stellar astrophysics and pulsar recycling.
3,224 citations
Johns Hopkins University1, Princeton University2, University of British Columbia3, Perimeter Institute for Theoretical Physics4, University of Minnesota5, Max Planck Society6, University of Toronto7, Institute for the Physics and Mathematics of the Universe8, Goddard Space Flight Center9, University of Chicago10, Brown University11, University of California, Los Angeles12
TL;DR: The final nine-year maps and basic results from the Wilkinson Microwave Anisotropy Probe (WMAP) mission are presented in this paper, where the authors present a highly constrained Lambda-CDM cosmological model with precise and accurate parameters.
Abstract: We present the final nine-year maps and basic results from the Wilkinson Microwave Anisotropy Probe (WMAP) mission. The full nine-year analysis of the time-ordered data provides updated characterizations and calibrations of the experiment. We also provide new nine-year full sky temperature maps that were processed to reduce the asymmetry of the effective beams. Temperature and polarization sky maps are examined to separate cosmic microwave background (CMB) anisotropy from foreground emission, and both types of signals are analyzed in detail.We provide new point source catalogs as well as new diffuse and point source foreground masks. An updated template-removal process is used for cosmological analysis; new foreground fits are performed, and new foreground reduced are presented.We nowimplement an optimal C(exp -1)1 weighting to compute the temperature angular power spectrum. The WMAP mission has resulted in a highly constrained Lambda-CDM cosmological model with precise and accurate parameters in agreement with a host of other cosmological measurements. When WMAP data are combined with finer scale CMB, baryon acoustic oscillation, and Hubble constant measurements, we find that big bang nucleosynthesis is well supported and there is no compelling evidence for a non-standard number of neutrino species (N(sub eff) = 3.84 +/- 0.40). The model fit also implies that the age of the universe is (sub 0) = 13.772 +/- 0.059 Gyr, and the fit Hubble constant is H(sub 0) = 69.32 +/- 0.80 km/s/ Mpc. Inflation is also supported: the fluctuations are adiabatic, with Gaussian random phases; the detection of a deviation of the scalar spectral index from unity, reported earlier by the WMAP team, now has high statistical significance (n(sub s) = 0.9608+/-0.0080); and the universe is close to flat/Euclidean (Omega = −0.0027+0.0039/−0.0038). Overall, the WMAP mission has resulted in a reduction of the cosmological parameter volume by a factor of 68,000 for the standard six-parameter Lambda-CDM model, based on CMB data alone. For a model including tensors, the allowed seven-parameter volume has been reduced by a factor 117,000. Other cosmological observations are in accord with the CMB predictions, and the combined data reduces the cosmological parameter volume even further.With no significant anomalies and an adequate goodness of fit, the inflationary flat Lambda-CDM model and its precise and accurate parameters rooted in WMAP data stands as the standard model of cosmology.
Chad J. Creighton1, Margaret Morgan1, Preethi H. Gunaratne1, Preethi H. Gunaratne2 +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.
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston Medical Center3, University of Zurich4, University of Missouri–Kansas City5, International Olympic Committee6, University of Oslo7, University of Toronto8, University of Michigan9, Vanderbilt University Medical Center10, University of Washington11, University of North Carolina at Chapel Hill12, University of British Columbia13, Cornell University14, Burke Rehabilitation Hospital15, University of Ottawa16, Medical College of Wisconsin17, University of New South Wales18, Monash University19, University of Melbourne20, McMaster University21, University of Medicine and Dentistry of New Jersey22, Princeton University23
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.
TL;DR: In this paper, the authors present the first comprehensive, multidisciplinary review of consumer rebates that includes federal regulations, state laws, and academic research, and identify federal guidelines for rebates by reviewing the 18 Federal Trade Commision rebate-related complaints and the associated consent decrees.
Abstract: The authors present the first comprehensive, multidisciplinary review of consumer rebates that includes federal regulations, state laws, and academic research. They discuss four topics that have been the foci of consumer concerns and policy reform: rebate advertising, rebate redemption disclosures, rebate redemption processes, and rebate payment processes. With respect to each of these four topics, the authors identify federal guidelines for rebates by reviewing the 18 Federal Trade Commision rebate-related complaints and the 18 associated consent decrees. Furthermore, they discuss 15 rebate laws from 11 U.S. states, 7 of which were enacted since 2007. In addition, they review academic research related to rebates from diverse literatures including marketing, consumer behavior, psychology, and economics and identify research gaps. This information should help policy makers evaluate rebate policies to assess whether the policies are evidence based, and it should help academics identify unanswered research q...
University of California, San Diego1, University of Western Ontario2, Katholieke Universiteit Leuven3, University of Chicago4, Icahn School of Medicine at Mount Sinai5, Lille University of Science and Technology6, Charles University in Prague7, University of Alberta8, University of Washington9, University of British Columbia10, Millennium Pharmaceuticals11
TL;DR: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolIZumab (rather than switching to placebo) were morelikely to be in remission at week 52.
Abstract: BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...
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.
Joint Genome Institute1, Bielefeld University2, University of Technology, Sydney3, University of California, Davis4, Bigelow Laboratory For Ocean Sciences5, University of British Columbia6, University of Nevada, Las Vegas7, University of Patras8, Woods Hole Oceanographic Institution9, University of Illinois at Urbana–Champaign10, University of Queensland11
TL;DR: This study applies single-cell genomics to target and sequence 201 archaeal and bacterial cells from nine diverse habitats belonging to 29 major mostly uncharted branches of the tree of life and provides a systematic step towards a better understanding of biological evolution on the authors' planet.
Abstract: Genome sequencing enhances our understanding of the biological world by providing blueprints for the evolutionary and functional diversity that shapes the biosphere. However, microbial genomes that are currently available are of limited phylogenetic breadth, owing to our historical inability to cultivate most microorganisms in the laboratory. We apply single-cell genomics to target and sequence 201 uncultivated archaeal and bacterial cells from nine diverse habitats belonging to 29 major mostly uncharted branches of the tree of life, so-called 'microbial dark matter'. With this additional genomic information, we are able to resolve many intra- and inter-phylum-level relationships and to propose two new superphyla. We uncover unexpected metabolic features that extend our understanding of biology and challenge established boundaries between the three domains of life. These include a novel amino acid use for the opal stop codon, an archaeal-type purine synthesis in Bacteria and complete sigma factors in Archaea similar to those in Bacteria. The single-cell genomes also served to phylogenetically anchor up to 20% of metagenomic reads in some habitats, facilitating organism-level interpretation of ecosystem function. This study greatly expands the genomic representation of the tree of life and provides a systematic step towards a better understanding of biological evolution on our planet.
TL;DR: It is suggested that poverty-related concerns consume mental resources, leaving less for other tasks, because poverty itself reduces cognitive capacity.
Abstract: The poor often behave in less capable ways, which can further perpetuate poverty. We hypothesize that poverty directly impedes cognitive function and present two studies that test this hypothesis. First, we experimentally induced thoughts about finances and found that this reduces cognitive performance among poor but not in well-off participants. Second, we examined the cognitive function of farmers over the planting cycle. We found that the same farmer shows diminished cognitive performance before harvest, when poor, as compared with after harvest, when rich. This cannot be explained by differences in time available, nutrition, or work effort. Nor can it be explained with stress: Although farmers do show more stress before harvest, that does not account for diminished cognitive performance. Instead, it appears that poverty itself reduces cognitive capacity. We suggest that this is because poverty-related concerns consume mental resources, leaving less for other tasks. These data provide a previously unexamined perspective and help explain a spectrum of behaviors among the poor. We discuss some implications for poverty policy.
TL;DR: The most comprehensive meta-analysis to date by synthesizing the results of 228 studies examining biological responses to ocean acidification reveals decreased survival, calcification, growth, development and abundance in response to acidification, and suggests that other factors, such as nutritional status or source population, could cause substantial variation in organisms' responses.
Abstract: Ocean acidification represents a threat to marine species worldwide, and forecasting the ecological impacts of acidification is a high priority for science, management, and policy. As research on the topic expands at an exponential rate, a comprehensive understanding of the variability in organisms' responses and corresponding levels of certainty is necessary to forecast the ecological effects. Here, we perform the most comprehensive meta-analysis to date by synthesizing the results of 228 studies examining biological responses to ocean acidification. The results reveal decreased survival, calcification, growth, development and abundance in response to acidification when the broad range of marine organisms is pooled together. However, the magnitude of these responses varies among taxonomic groups, suggesting there is some predictable trait-based variation in sensitivity, despite the investigation of approximately 100 new species in recent research. The results also reveal an enhanced sensitivity of mollusk larvae, but suggest that an enhanced sensitivity of early life history stages is not universal across all taxonomic groups. In addition, the variability in species' responses is enhanced when they are exposed to acidification in multi-species assemblages, suggesting that it is important to consider indirect effects and exercise caution when forecasting abundance patterns from single-species laboratory experiments. Furthermore, the results suggest that other factors, such as nutritional status or source population, could cause substantial variation in organisms' responses. Last, the results highlight a trend towards enhanced sensitivity to acidification when taxa are concurrently exposed to elevated seawater temperature.
New York University1, University of Amsterdam2, Shiga University of Medical Science3, Kyungpook National University4, St George's, University of London5, Children's National Medical Center6, Leiden University7, University of Barcelona8, University of Oulu9, Vanderbilt University10, University of British Columbia11, University of Paris12, University of Rochester13, University of Pavia14, Nippon Medical School15, Johns Hopkins University16, Washington University in St. Louis17
TL;DR: Developed in partnership with the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology, and the Asia Pacific Heart Rhythm society (APHRS).
Commonwealth Scientific and Industrial Research Organisation1, University of Queensland2, University of Erlangen-Nuremberg3, Museum für Naturkunde4, Nelson Mandela Metropolitan University5, University of the Sunshine Coast6, 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
University of British Columbia1, University of Toronto2, McGill University3, Dalhousie University4, University of Calgary5, University of Western Ontario6, Queen's University7, McMaster University8, University of São Paulo9, University of Pittsburgh10, Seoul National University11, University of Melbourne12, Deakin University13
TL;DR: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009, and this third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunctionWith the previous publications.
Abstract: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.
University of Oxford1, World Animal Protection2, University of Cambridge3, University of East Anglia4, University of Leeds5, Oxfam6, Food and Agriculture Organization7, University of British Columbia8, Commonwealth Scientific and Industrial Research Organisation9, University of Aberdeen10, CGIAR11, International Institute for Environment and Development12
TL;DR: Clearer understanding is needed of the premises underlying SI and how it relates to food-system priorities and climate change poses challenges to agriculture.
Abstract: Food security is high on the global policy agenda. Demand for food is increasing as populations grow and gain wealth to purchase more varied and resource-intensive diets. There is increased competition for land, water, energy, and other inputs into food production. Climate change poses challenges to agriculture, particularly in developing countries ( 1 ), and many current farming practices damage the environment and are a major source of greenhouse gases (GHG). In an increasingly globalized world, food insecurity in one region can have widespread political and economic ramifications ( 2 ).
Science for Life Laboratory1, Umeå University2, Sant'Anna School of Advanced Studies3, Ghent University4, Royal Institute of Technology5, University of Udine6, Swedish University of Agricultural Sciences7, University of Jena8, Uppsala University9, Children's Hospital Oakland10, University of British Columbia11, University of Valencia12, Laval University13, Stockholm University14, Norwegian University of Life Sciences15
TL;DR: The draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm, is presented, revealing numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs, which opens up new genomic avenues for conifer forestry and breeding.
Abstract: Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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.
Wageningen University and Research Centre1, Lancaster University2, Indiana University3, University of Pennsylvania4, Stanford University5, Swedish University of Agricultural Sciences6, University of British Columbia7, Utah State University8, University of Tennessee9, University of California, Berkeley10
TL;DR: In this paper, a plant-soil feedback model is proposed to explain succession, invasion, response to climate warming and diversity-productivity relationships in terrestrial ecosystems, and how terrestrial ecosystems respond to global land use and climate change.
Abstract: Summary
Plant–soil feedbacks is becoming an important concept for explaining vegetation dynamics, the invasiveness of introduced exotic species in new habitats and how terrestrial ecosystems respond to global land use and climate change. Using a new conceptual model, we show how critical alterations in plant–soil feedback interactions can change the assemblage of plant communities. We highlight recent advances, define terms and identify future challenges in this area of research and discuss how variations in strengths and directions of plant–soil feedbacks can explain succession, invasion, response to climate warming and diversity-productivity relationships.
While there has been a rapid increase in understanding the biological, chemical and physical mechanisms and their interdependencies underlying plant–soil feedback interactions, further progress is to be expected from applying new experimental techniques and technologies, linking empirical studies to modelling and field-based studies that can include plant–soil feedback interactions on longer time scales that also include long-term processes such as litter decomposition and mineralization.
Significant progress has also been made in analysing consequences of plant–soil feedbacks for biodiversity-functioning relationships, plant fitness and selection.
To further integrate plant–soil feedbacks into ecological theory, it will be important to determine where and how observed patterns may be generalized, and how they may influence evolution.
Synthesis. Gaining a greater understanding of plant–soil feedbacks and underlying mechanisms is improving our ability to predict consequences of these interactions for plant community composition and productivity under a variety of conditions. Future research will enable better prediction and mitigation of the consequences of human-induced global changes, improve efforts of restoration and conservation and promote sustainable provision of ecosystem services in a rapidly changing world.
TL;DR: A comprehensive review highlights recent advances in understanding of the intestinal pathotypes of E. coli, which carry an enormous potential to cause disease and continue to present challenges to human health.
Abstract: Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli.
University of Lisbon1, Commonwealth Scientific and Industrial Research Organisation2, Virginia Tech College of Natural Resources and Environment3, California Institute of Technology4, Wageningen University and Research Centre5, Cardiff University6, American Museum of Natural History7, BirdLife International8, University of British Columbia9, Food and Agriculture Organization10, Australian Museum11, Leibniz Association12, Royal Society for the Protection of Birds13, University of Maryland, College Park14, Yale University15, Stanford University16, Monash University17, Kyoto University18, Zoological Society of London19, United States Geological Survey20, United Nations Environment Programme21, University of Sussex22, International Union for Conservation of Nature and Natural Resources23, Office of Environment and Heritage24
TL;DR: With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners are developing—and seeking consensus around—Essential Biod diversity Variables (EBVs) that could form the basis of monitoring programs worldwide.
Abstract: Reducing the rate of biodiversity loss and averting dangerous biodiversity change are international goals, reasserted by the Aichi Targets for 2020 by Parties to the United Nations (UN) Convention on Biological Diversity (CBD) after failure to meet the 2010 target (1, 2). However, there is no global, harmonized observation system for delivering regular, timely data on biodiversity change (3). With the first plenary meeting of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) soon under way, partners from the Group on Earth Observations Biodiversity Observation Network (GEO BON) (4) are developing—and seeking consensus around—Essential Biodiversity Variables (EBVs) that could form the basis of monitoring programs worldwide.
Cornell University1, Ford Motor Company2, Virginia Mason Medical Center3, University of British Columbia4, Johns Hopkins University5, Bon Secours Health System6, University of Texas Health Science Center at San Antonio7, University of Colorado Denver8, University of Miami9, Duke University10, University of Toronto11, Monash University12, University of Florida13
TL;DR: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribvirin was effective.
Abstract: A B S T R AC T BACKGROUND Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peg interferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treat ment, as compared with 73% with 16 weeks of treatment (difference, −23 percent age points; 95% CI, −35 to −11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS In patients with HCV genotype 2 or 3 infection for whom treatment with peginter feron and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbu vir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)