Showing papers by "University of Kiel published in 2020"
Queen's University Belfast1, University of St Andrews2, Aix-Marseille University3, Historic England4, University of Sheffield5, University of Oxford6, Alfred Wegener Institute for Polar and Marine Research7, University of Minnesota8, Xi'an Jiaotong University9, Nanjing Normal University10, University of Hohenheim11, University of Kiel12, University of California, Santa Cruz13, Lawrence Livermore National Laboratory14, ETH Zurich15, University of Waikato16, Woods Hole Oceanographic Institution17, Heidelberg University18, Cornell University19, Lund University20, University of New South Wales21, University of Arizona22, University of Groningen23, University of Bristol24, University of Glasgow25, University of California, Irvine26, University of Bern27, Aarhus University28, Nagoya University29, Swiss Federal Institute for Forest, Snow and Landscape Research30, National Museum of Japanese History31, University of Bologna32
TL;DR: In this article, the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP.
Abstract: Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
2,800 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: A 3p21.31 gene cluster is identified as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and a potential involvement of the ABO blood-group system is confirmed.
Abstract: Background There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19) Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19 Methods We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels Results We detected cross-replicating associations with rs11385942 at locus 3p2131 and with rs657152 at locus 9q342, which were significant at the genomewide level (P Conclusions We identified a 3p2131 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system (Funded by Stein Erik Hagen and others)
1,529 citations
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
University of Hohenheim1, University of Göttingen2, German Institute of Global and Area Studies3, International Maize and Wheat Improvement Center4, University of Bern5, Magister6, University of Waikato7, University of Jena8, Bogor Agricultural University9, University of Kiel10, Leipzig University11, University of the Philippines Los Baños12, Russian Academy of Sciences13, Tadulako University14
TL;DR: Landscape compositions that can mitigate trade-offs under optimal land-use allocation but also show that intensive monocultures always lead to higher profits are identified, suggesting that targeted landscape planning is needed to increase land- use efficiency while ensuring socio-ecological sustainability.
Abstract: Land-use transitions can enhance the livelihoods of smallholder farmers but potential economic-ecological trade-offs remain poorly understood. Here, we present an interdisciplinary study of the environmental, social and economic consequences of land-use transitions in a tropical smallholder landscape on Sumatra, Indonesia. We find widespread biodiversity-profit trade-offs resulting from land-use transitions from forest and agroforestry systems to rubber and oil palm monocultures, for 26,894 aboveground and belowground species and whole-ecosystem multidiversity. Despite variation between ecosystem functions, profit gains come at the expense of ecosystem multifunctionality, indicating far-reaching ecosystem deterioration. We identify landscape compositions that can mitigate trade-offs under optimal land-use allocation but also show that intensive monocultures always lead to higher profits. These findings suggest that, to reduce losses in biodiversity and ecosystem functioning, changes in economic incentive structures through well-designed policies are urgently needed.
697 citations
University of Sheffield1, Alfred Wegener Institute for Polar and Marine Research2, Aix-Marseille University3, Queen's University Belfast4, University of St Andrews5, University of Oxford6, University of Kiel7, Woods Hole Oceanographic Institution8, Heidelberg University9, Williams College10, Aarhus University11, University of Cambridge12
TL;DR: Marine20 as mentioned in this paper is an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radioccarbon from 0 −55 cal kBP and serves as a baseline for regional oceanic variation.
Abstract: The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.
690 citations
University of Bremen1, Potsdam Institute for Climate Impact Research2, University of Potsdam3, University College London4, University of Padua5, Leibniz Institute of Marine Sciences6, University of St Andrews7, University of Exeter8, National Oceanography Centre, Southampton9, National Institute of Geophysics and Volcanology10, University of Cambridge11, University of Kiel12, University of Edinburgh13, University of Bristol14, Utrecht University15, Oregon State University16, Tongji University17, University of Hawaii18, University of California, Santa Cruz19
TL;DR: A new, highly resolved, astronomically dated, continuous composite of benthic foraminifer isotope records developed in the authors' laboratories reveals the key role that polar ice volume plays in the predictability of Cenozoic climate dynamics.
Abstract: Much of our understanding of Earth's past climate comes from the measurement of oxygen and carbon isotope variations in deep-sea benthic foraminifera. Yet, long intervals in existing records lack the temporal resolution and age control needed to thoroughly categorize climate states of the Cenozoic era and to study their dynamics. Here, we present a new, highly resolved, astronomically dated, continuous composite of benthic foraminifer isotope records developed in our laboratories. Four climate states-Hothouse, Warmhouse, Coolhouse, Icehouse-are identified on the basis of their distinctive response to astronomical forcing depending on greenhouse gas concentrations and polar ice sheet volume. Statistical analysis of the nonlinear behavior encoded in our record reveals the key role that polar ice volume plays in the predictability of Cenozoic climate dynamics.
655 citations
University of Waterloo1, National Technical University of Athens2, University of Alaska Fairbanks3, École Polytechnique Fédérale de Lausanne4, University of Kiel5, RMIT University6, University of St. Thomas (Minnesota)7, Nanyang Technological University8, Pacific Northwest National Laboratory9, Microsoft10, University of South Florida11, University of Chile12, South Dakota State University13
TL;DR: In this paper, definitions and classification of microgrid stability are presented and discussed, considering pertinent microgrid features such as voltage-frequency dependence, unbalancing, low inertia, and generation intermittency.
Abstract: This document is a summary of a report prepared by the IEEE PES Task Force (TF) on Microgrid Stability Definitions, Analysis, and Modeling, IEEE Power and Energy Society, Piscataway, NJ, USA, Tech. Rep. PES-TR66, Apr. 2018, which defines concepts and identifies relevant issues related to stability in microgrids. In this paper, definitions and classification of microgrid stability are presented and discussed, considering pertinent microgrid features such as voltage-frequency dependence, unbalancing, low inertia, and generation intermittency. A few examples are also presented, highlighting some of the stability classes defined in this paper. Further examples, along with discussions on microgrid components modeling and stability analysis tools can be found in the TF report.
403 citations
European Space Agency1, Goddard Space Flight Center2, INAF3, Université Paris-Saclay4, Royal Observatory of Belgium5, Imperial College London6, United States Naval Research Laboratory7, University of California, Berkeley8, Paris Diderot University9, University College London10, University of Liège11, University of Alcalá12, Kyung Hee University13, Max Planck Society14, University of Oslo15, Rutherford Appleton Laboratory16, ETH Zurich17, Southwest Research Institute18, Hoffmann-La Roche19, Spanish National Research Council20, University of Kiel21, University of California, Los Angeles22
TL;DR: The first mission of ESA's Cosmic Vision 2015-2025 programme and a mission of international collaboration between ESA and NASA, was launched on 10 February 2020 04:03 UTC from Cape Canaveral and aims to address key questions of solar and heliospheric physics pertaining to how the Sun creates and controls the Heliosphere, and why solar activity changes with time.
Abstract: Aims. Solar Orbiter, the first mission of ESA’s Cosmic Vision 2015–2025 programme and a mission of international collaboration between ESA and NASA, will explore the Sun and heliosphere from close up and out of the ecliptic plane. It was launched on 10 February 2020 04:03 UTC from Cape Canaveral and aims to address key questions of solar and heliospheric physics pertaining to how the Sun creates and controls the Heliosphere, and why solar activity changes with time. To answer these, the mission carries six remote-sensing instruments to observe the Sun and the solar corona, and four in-situ instruments to measure the solar wind, energetic particles, and electromagnetic fields. In this paper, we describe the science objectives of the mission, and how these will be addressed by the joint observations of the instruments onboard.Methods. The paper first summarises the mission-level science objectives, followed by an overview of the spacecraft and payload. We report the observables and performance figures of each instrument, as well as the trajectory design. This is followed by a summary of the science operations concept. The paper concludes with a more detailed description of the science objectives.Results. Solar Orbiter will combine in-situ measurements in the heliosphere with high-resolution remote-sensing observations of the Sun to address fundamental questions of solar and heliospheric physics. The performance of the Solar Orbiter payload meets the requirements derived from the mission’s science objectives. Its science return will be augmented further by coordinated observations with other space missions and ground-based observatories.
330 citations
TL;DR: The existence of brain-first and body-first subtypes of Parkinson's disease is supported by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups using multimodal imaging.
Abstract: Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner However, it remains uncertain where the initial α-synuclein aggregates originate We have hypothesized that Parkinson's disease comprises two subtypes A brain-first (top-down) type, where α-synuclein pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system; and a body-first (bottom-up) type, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain We also hypothesized that isolated REM sleep behaviour disorder (iRBD) is a prodromal phenotype for the body-first type Using multimodal imaging, we tested the hypothesis by quantifying neuronal dysfunction in structures corresponding to Braak stages I, II and III involvement in three distinct patient groups We included 37 consecutive de novo patients with Parkinson's disease into this case-control PET study Patients with Parkinson's disease were divided into 24 RBD-negative (PDRBD-) and 13 RBD-positive cases (PDRBD+) and a comparator group of 22 iRBD patients We used 11C-donepezil PET/CT to assess cholinergic (parasympathetic) innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure the integrity of locus coeruleus pigmented neurons, and 18F-dihydroxyphenylalanine (FDOPA) PET to assess putaminal dopamine storage capacity Colon volume and transit times were assessed with CT scans and radiopaque markers Imaging data from the three groups were interrogated with ANOVA and Kruskal-Wallis tests corrected for multiple comparisons The PDRBD- and PDRBD+ groups showed similar marked reductions in putaminal FDOPA-specific uptake, whereas two-thirds of iRBD patients had normal scans (P < 10-13, ANOVA) When compared to the PDRBD- patients, the PDRBD+ and iRBD patients showed reduced mean MIBG heart:mediastinum ratios (P < 10-5, ANOVA) and colon 11C-donepezil standard uptake values (P = 0008, ANOVA) The PDRBD+ group trended towards a reduced mean MRI locus coeruleus: pons ratio compared to PDRBD- (P = 007, t-test) In comparison to the other groups, the PDRBD+ group also had enlarged colon volumes (P < 0001, ANOVA) and delayed colonic transit times (P = 001, Kruskal-Wallis) The combined iRBD and PDRBD+ patient data were compatible with a body-first trajectory, characterized by initial loss of cardiac MIBG signal and 11C-colonic donepezil signal followed by loss of putaminal FDOPA uptake In contrast, the PDRBD- data were compatible with a brain-first trajectory, characterized by primary loss of putaminal FDOPA uptake followed by a secondary loss of cardiac MIBG signal and 11C-donepezil signal These findings support the existence of brain-first and body-first subtypes of Parkinson's disease
320 citations
TL;DR: In the past 30 years, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially, particularly in low-income and middle-income countries, and further increases are expected globally as a result of population growth and ageing.
Abstract: Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. In the past 30 years, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially, particularly in low-income and middle-income countries, and further increases are expected globally as a result of population growth and ageing. This rise in absolute numbers of people affected suggests that advances in prevention and management of major neurological disorders are not sufficiently effective to counter global demographic changes. Urgent measures to reduce this burden are therefore needed. Because resources for health care and research are already overstretched, priorities need to be set to guide policy makers, governments, and funding organisations to develop and implement action plans for prevention, health care, and research to tackle the growing challenge of neurological disorders.
TL;DR: The World Karst Aquifer Map (WOKAM) as discussed by the authors is the first detailed and complete global geodatabase concerning the distribution of karstifiable rocks (carbonates and evaporites) representing potential karast aquifers.
Abstract: Karst regions offer a variety of natural resources such as freshwater and biodiversity, and many cultural resources. The World Karst Aquifer Map (WOKAM) is the first detailed and complete global geodatabase concerning the distribution of karstifiable rocks (carbonates and evaporites) representing potential karst aquifers. This study presents a statistical evaluation of WOKAM, focusing entirely on karst in carbonate rocks and addressing four main aspects: (1) global occurrence and geographic distribution of karst; (2) karst in various topographic settings and coastal areas; (3) karst in different climatic zones; and (4) populations living on karst. According to the analysis, 15.2% of the global ice-free continental surface is characterized by the presence of karstifiable carbonate rock. The largest percentage is in Europe (21.8%); the largest absolute area occurs in Asia (8.35 million km2). Globally, 31.1% of all surface exposures of carbonate rocks occur in plains, 28.1% in hills and 40.8% in mountains, and 151,400 km or 15.7% of marine coastlines are characterized by carbonate rocks. About 34.2% of all carbonate rocks occur in arid climates, followed by 28.2% in cold and 15.9% in temperate climates, whereas only 13.1 and 8.6% occur in tropical and polar climates, respectively. Globally, 1.18 billion people (16.5% of the global population) live on karst. The highest absolute number occurs in Asia (661.7 million), whereas the highest percentages are in Europe (25.3%) and North America (23.5%). These results demonstrate the global importance of karst and serve as a basis for further research and international water management strategies.
TL;DR: It is concluded that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.
TL;DR: The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond classical immune cells and may serve as an entry point to develop biomarkers and targeted treatments of patients with COVID-19.
TL;DR: In this article, a review of the recent state-of-the-art achievements in the field of plasmonic biosensing based terahertz spectroscopy is presented.
TL;DR: These findings identify low avidity CD4+T cell responses as a hallmark of severe COVID-19, and argue against a protective role for CCCoV reactive T cells in SARS-CoV-2 infection.
TL;DR: The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country.
Abstract: Summary Background Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide. Methods The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates. Findings In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5–23·9) in the EU and 41·1 million (36·7–45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09–1·14) in the EU and 1·97 million (1·95–2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3–17·1) of total DALYs and 19·5% (18·0–21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80–84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs. Interpretation Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries. Funding European Academy of Neurology.
Imperial College London1, University of Exeter2, Broad Institute3, United States Geological Survey4, University of California, Riverside5, Max Planck Society6, University of Kiel7, University of Toronto8, Manchester Academic Health Science Centre9, University of Wisconsin-Madison10, University of British Columbia11, McGill University12, University of California, Berkeley13, McMaster University14, Duke University15, Johns Hopkins University16
TL;DR: P poignant examples of emerging fungal threats in each of three areas: human health, wildlife biodiversity, and food security are focused on.
Abstract: The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been reported to infect vertebrates, 200 of which can be human associated, either as commensals and members of our microbiome or as pathogens that cause infectious diseases. These organisms pose a growing threat to human health with the global increase in the incidence of invasive fungal infections, prevalence of fungal allergy, and the evolution of fungal pathogens resistant to some or all current classes of antifungals. More broadly, there has been an unprecedented and worldwide emergence of fungal pathogens affecting animal and plant biodiversity. Approximately 8,000 species of fungi and Oomycetes are associated with plant disease. Indeed, across agriculture, such fungal diseases of plants include new devastating epidemics of trees and jeopardize food security worldwide by causing epidemics in staple and commodity crops that feed billions. Further, ingestion of mycotoxins contributes to ill health and causes cancer. Coordinated international research efforts, enhanced technology translation, and greater policy outreach by scientists are needed to more fully understand the biology and drivers that underlie the emergence of fungal diseases and to mitigate against their impacts. Here, we focus on poignant examples of emerging fungal threats in each of three areas: human health, wildlife biodiversity, and food security.
Charité1, University of Oxford2, French Institute of Health and Medical Research3, University Hospital Regensburg4, Guy's and St Thomas' NHS Foundation Trust5, University of California, San Francisco6, Harvard University7, University of Wisconsin-Madison8, King's College London9, Fraunhofer Society10, University of Regensburg11, Beckman Coulter12, Miltenyi Biotec13, University of Kiel14, Duke University15, Bellvitge University Hospital16, Royal College of Surgeons of England17, St Mary's Hospital18, Vita-Salute San Raffaele University19
TL;DR: In this paper, the authors evaluated the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment in kidney transplant patients and found that CBMP is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year.
Goddard Space Flight Center1, Creighton University2, University of Tartu3, Wisconsin Department of Natural Resources4, Vietnam National University, Hanoi5, University of Tsukuba6, United States Naval Research Laboratory7, University of Wisconsin-Madison8, University of Waikato9, National Oceanic and Atmospheric Administration10, University of Kiel11, Silver Spring Networks12
TL;DR: In this paper, a machine-learning model, the Mixture Density Network (MDN), was proposed for consistent, cross-mission retrievals of near-surface concentration of chlorophyll-a (Chla) in various aquatic ecosystems with broad ranges of trophic levels.
University Medical Center Groningen1, Erasmus University Rotterdam2, Katholieke Universiteit Leuven3, Chinese Academy of Sciences4, University of Surrey5, King's College London6, University of Toronto7, Mount Sinai Hospital8, Avera Health9, Karolinska Institutet10, Saint Petersburg State University of Information Technologies, Mechanics and Optics11, University of Copenhagen12, Greifswald University Hospital13, University of Kiel14, Albert Einstein College of Medicine15, Sungkyunkwan University16, University of Tartu17, Weizmann Institute of Science18, Copenhagen University Hospital19, University of Texas Health Science Center at Houston20, University of Alabama at Birmingham21, Stockholm University22, University of Michigan23, VU University Amsterdam24, University of Oxford25, University of Bristol26, University of Amsterdam27, Maastricht University28, University of California, San Diego29, University of Eastern Finland30, National Institutes of Health31, University of California, Berkeley32, University of Milan33, Harvard University34, Radboud University Nijmegen35, University of North Carolina at Chapel Hill36, Ewha Womans University37, Fred Hutchinson Cancer Research Center38, National Research Council39
TL;DR: A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome has causal effects in ulcerative colitis and rheumatoid arthritis.
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 out of 410 genera were detected in more than 95% samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 31 loci affecting microbiome at a genome-wide significant (P
TL;DR: The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA.
Abstract: Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.
TL;DR: The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.
Abstract: Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.
University of British Columbia1, Memorial University of Newfoundland2, University of Paris3, National Autonomous University of Mexico4, Scottish Association for Marine Science5, École Normale Supérieure6, University of Kiel7, University of Tasmania8, Woods Hole Oceanographic Institution9, Leibniz Institute for Neurobiology10, University of East Anglia11, Ocean Conservancy12, UNESCO13, Instituto Politécnico Nacional14, Alfred Wegener Institute for Polar and Marine Research15, University of São Paulo16, Centre national de la recherche scientifique17
TL;DR: In this article, the authors recommend key strategies to address these challenges, including stronger integration of sciences and ocean-observing systems, improved science-policy interfaces, new partnerships supported by a new ocean-climate finance system, and improved ocean literacy and education to modify social norms and behaviors.
Abstract: The health of the ocean, central to human well-being, has now reached a critical point. Most fish stocks are overexploited, climate change and increased dissolved carbon dioxide are changing ocean chemistry and disrupting species throughout food webs, and the fundamental capacity of the ocean to regulate the climate has been altered. However, key technical, organizational, and conceptual scientific barriers have prevented the identification of policy levers for sustainability and transformative action. Here, we recommend key strategies to address these challenges, including (1) stronger integration of sciences and (2) ocean-observing systems, (3) improved science-policy interfaces, (4) new partnerships supported by (5) a new ocean-climate finance system, and (6) improved ocean literacy and education to modify social norms and behaviors. Adopting these strategies could help establish ocean science as a key foundation of broader sustainability transformations.
TL;DR: Patients with previously untreated chronic lymphocytic leukaemia given venetoclax plus obinutuzumab had a significantly longer progression-free survival than did patients given chlorambucilplus obinutsumab, and Median progression- free survival was not reached.
Abstract: Summary Background Venetoclax plus obinutuzumab has been established as a fixed-duration treatment regimen for patients with chronic lymphocytic leukaemia. We compared the long-term efficacy after treatment cessation of the combination of venetoclax plus obinutuzumab with chlorambucil plus obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia. Methods CLL14 is a multicentre, randomised, open-label, phase 3 trial done at 196 sites in 21 countries. Eligible patients were aged 18 years or older, had untreated chronic lymphocytic leukaemia, and coexisting conditions with a cumulative illness rating scale greater than 6, a creatinine clearance of 30–69 mL/min, or both. Patients were randomly assigned (1:1) via a web and voicemail system with allocation concealment and based on a computer-generated randomisation schedule with a block size of six and stratified by Binet stage and geographical region. Patients received either venetoclax plus obinutuzumab (oral venetoclax initiated on day 22 of cycle 1 [28-day cycles], with a 5-week dose ramp-up [20 mg, 50 mg, 100 mg, and 200 mg, then 400 mg daily for 1 week], thereafter continuing at 400 mg daily until completion of cycle 12; combined with intravenous obinutuzumab for six cycles starting with 100 mg on day 1 and 900 mg on day 2 [or 1000 mg on day 1], 1000 mg on days 8 and day 15 of cycle 1, and subsequently 1000 mg on day 1 of cycles 2 through 6) or chlorambucil plus obinutuzumab (oral chlorambucil at 0·5 mg/kg bodyweight on days 1 and 15 of each cycle for 12 cycles combined with the same obinutuzumab regimen). The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. Patient enrolment is complete, and the study is registered with ClinicalTrails.gov , NCT02242942 . Findings Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (n=216) or chlorambucil plus obinutuzumab (n=216). All patients had been off treatment for at least 24 months at data collection. At a median follow-up of 39·6 months (IQR 36·8–43·0), patients given venetoclax plus obinutuzumab had a significantly longer progression-free survival than did patients given chlorambucil plus obinutuzumab (HR 0·31, 95% CI 0·22–0·44; p Interpretation 2 years after treatment cessation, venetoclax plus obinutuzumab continues to significantly improve progression-survival compared with chlorambucil plus obinutuzumab, thereby providing a limited duration treatment option for patients with previously untreated chronic lymphocytic leukaemia. Funding F Hoffmann-La Roche and AbbVie.
Columbia University1, Allen Institute for Brain Science2, University of Copenhagen3, Carleton University4, George Mason University5, Technical University of Madrid6, Max Planck Society7, University of Oxford8, Aarhus University9, Harvard University10, University of Edinburgh11, VU University Amsterdam12, Cajal Institute13, Vanderbilt University14, Scuola Normale Superiore di Pisa15, University of Kiel16, École Polytechnique Fédérale de Lausanne17, Ruhr University Bochum18, Novartis19, Karolinska Institutet20, Cold Spring Harbor Laboratory21, Massachusetts Institute of Technology22, RWTH Aachen University23, University of Western Ontario24, Leiden University25, Stanford University26, King's College London27, University of Haifa28, Charles University in Prague29, Bar-Ilan University30, Macquarie University31, J. Craig Venter Institute32, Spanish National Research Council33, University of Göttingen34, University of Szeged35, Baylor College of Medicine36, University of Strathclyde37, New York University38
TL;DR: This work proposes the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex that should be hierarchical and use a standardized nomenclature, and could serve as an example for cell type atlases in other parts of the body.
Abstract: To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.
TL;DR: The results identify a mechanism of neuronal death post-infection and point to a role for tissue-resident MMs in limiting neuronal damage.
TL;DR: The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported, and the hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0·23 (97·5% CI 0·12-0·45; p<0·0001).
University of Kiel1, Tel Aviv Sourasky Medical Center2, Rush University Medical Center3, Tel Aviv University4, École Polytechnique Fédérale de Lausanne5, University Medical Center Groningen6, University of Cincinnati7, Radboud University Nijmegen8, Saarland University9, Stanford University10, University of Brescia11, Newcastle University12, National Health Service13
TL;DR: Clinicians and researchers should consider disparities in the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, and the multiple factors that contribute to them.
Abstract: Mobile health technologies (wearable, portable, body-fixed sensors, or domestic-integrated devices) that quantify mobility in unsupervised, daily living environments are emerging as complementary clinical assessments. Data collected in these ecologically valid, patient-relevant settings can overcome limitations of conventional clinical assessments, as they capture fluctuating and rare events. These data could support clinical decision making and could also serve as outcomes in clinical trials. However, studies that directly compared assessments made in unsupervised and supervised (eg, in the laboratory or hospital) settings point to large disparities, even in the same parameters of mobility. These differences appear to be affected by psychological, physiological, cognitive, environmental, and technical factors, and by the types of mobilities and diagnoses assessed. To facilitate the successful adaptation of the unsupervised assessment of mobility into clinical practice and clinical trials, clinicians and researchers should consider these disparities and the multiple factors that contribute to them.
Masaryk University1, Zurich University of Applied Sciences/ZHAW2, University of Bayreuth3, Spanish National Research Council4, Murdoch University5, Stellenbosch University6, University of Belgrade7, Sapienza University of Rome8, University of Göttingen9, University of the Basque Country10, Free University of Bozen-Bolzano11, Russian Academy of Sciences12, Martin Luther University of Halle-Wittenberg13, University of Nova Gorica14, Slovenian Academy of Sciences and Arts15, University of Novi Sad16, Research Institute for Nature and Forest17, University of Western Brittany18, National Academy of Sciences of Ukraine19, Slovak Academy of Sciences20, Complutense University of Madrid21, University of Lorraine22, University of Catania23, Transilvania University of Brașov24, University of Bremen25, University of Rostock26, Radboud University Nijmegen27, Mendel University28, University of Wrocław29, Karabük University30, Keldysh Institute of Applied Mathematics31, Kazan Federal University32, Forest Research Institute33, Centre national de la recherche scientifique34, Alexandru Ioan Cuza University35, Shirshov Institute of Oceanology36, University of Vic37, University of Barcelona38, University of Agriculture, Faisalabad39, University of Latvia40, University of Kiel41, University of Zagreb42, University of Molise43, Bulgarian Academy of Sciences44, University of Vienna45, European Environment Agency46
TL;DR: This article developed the classification expert system EUNIS-ESy, which assigns vegetation plots to European habitats based on their species composition and geographic location. But the system is not suitable for outdoor gardening.
Abstract: EUNIS Habitat Classification is a standard classification of European habitats. We developed the classification expert system EUNIS‐ESy, which assigns vegetation plots to EUNIS habitats based on their species composition and geographic location. We classified 1,261,373 vegetation plots from the European Vegetation Archive and determined characteristic species combinations and prepared distribution maps for 199 habitats at Level 3 of EUNIS hierarchy.