Showing papers by "Pompeu Fabra University published in 2021"
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Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
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National Institutes of Health1, University of Cambridge2, Wellcome Trust Sanger Institute3, Rockefeller University4, University of California, Davis5, Leibniz Association6, Seoul National University7, University of Southern California8, European Bioinformatics Institute9, Max Planck Society10, Dresden University of Technology11, Radboud University Nijmegen12, University of St Andrews13, University of Massachusetts Amherst14, University of Adelaide15, University of Missouri16, East Carolina University17, University of Queensland18, Clemson University19, University of Otago20, University of Arizona21, Natural History Museum22, Bangor University23, University of Konstanz24, Harvard University25, Northeastern University26, National Museum of Natural History27, University of Antwerp28, University of Graz29, University of Florida30, University of Basel31, University of California, Santa Cruz32, Zoological Society of San Diego33, Pacific Biosciences34, Pompeu Fabra University35, University of Maryland, College Park36, Harbin Institute of Technology37, University of Chicago38, Oregon Health & Science University39, Monash University Malaysia Campus40, Qatar Airways41, University of Milan42, Goethe University Frankfurt43, Pennsylvania State University44, University of Los Andes45, University of Copenhagen46, Norwegian University of Science and Technology47, Agency for Science, Technology and Research48, Royal Ontario Museum49, Smithsonian Institution50, Howard Hughes Medical Institute51, Walter Reed Army Institute of Research52, University of East Anglia53, University College Dublin54, University of Illinois at Urbana–Champaign55, La Trobe University56, University of California, San Diego57, Nova Southeastern University58
TL;DR: The Vertebrate Genomes Project (VGP) as mentioned in this paper is an international effort to generate high quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
Abstract: High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
647 citations
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TL;DR: The authors review the role of RBPs in human genetic disorders, both Mendelian and somatic, discuss the molecular mechanisms of disease and highlight emerging therapeutic interventions that target RBPs.
Abstract: RNA-binding proteins (RBPs) are critical effectors of gene expression, and as such their malfunction underlies the origin of many diseases. RBPs can recognize hundreds of transcripts and form extensive regulatory networks that help to maintain cell homeostasis. System-wide unbiased identification of RBPs has increased the number of recognized RBPs into the four-digit range and revealed new paradigms: from the prevalence of structurally disordered RNA-binding regions with roles in the formation of membraneless organelles to unsuspected and potentially pervasive connections between intermediary metabolism and RNA regulation. Together with an increasingly detailed understanding of molecular mechanisms of RBP function, these insights are facilitating the development of new therapies to treat malignancies. Here, we provide an overview of RBPs involved in human genetic disorders, both Mendelian and somatic, and discuss emerging aspects in the field with emphasis on molecular mechanisms of disease and therapeutic interventions.
304 citations
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TL;DR: SPOTlight deconvolution of the mouse brain correctly mapped subtle neuronal cell states of the cortical layers and the defined architecture of the hippocampus and in human pancreatic cancer, it successfully segmented patient sections and further fine-mapped normal and neoplastic cell states.
Abstract: Spatially resolved gene expression profiles are key to understand tissue organization and function. However, spatial transcriptomics (ST) profiling techniques lack single-cell resolution and require a combination with single-cell RNA sequencing (scRNA-seq) information to deconvolute the spatially indexed datasets. Leveraging the strengths of both data types, we developed SPOTlight, a computational tool that enables the integration of ST with scRNA-seq data to infer the location of cell types and states within a complex tissue. SPOTlight is centered around a seeded non-negative matrix factorization (NMF) regression, initialized using cell-type marker genes and non-negative least squares (NNLS) to subsequently deconvolute ST capture locations (spots). Simulating varying reference quantities and qualities, we confirmed high prediction accuracy also with shallowly sequenced or small-sized scRNA-seq reference datasets. SPOTlight deconvolution of the mouse brain correctly mapped subtle neuronal cell states of the cortical layers and the defined architecture of the hippocampus. In human pancreatic cancer, we successfully segmented patient sections and further fine-mapped normal and neoplastic cell states. Trained on an external single-cell pancreatic tumor references, we further charted the localization of clinical-relevant and tumor-specific immune cell states, an illustrative example of its flexible application spectrum and future potential in digital pathology.
251 citations
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Free University of Berlin1, Hospital Kuala Lumpur2, Cleveland Clinic3, Mater Dei Hospital4, Kantonsspital St. Gallen5, University of Zurich6, Medical University of Vienna7, Montreal Children's Hospital8, University of Cincinnati9, University of Southern Denmark10, Technische Universität München11, Opole University12, Federal University of Paraná13, University of Southampton14, Federal University of São Paulo15, New York University16, University of Debrecen17, Istanbul University18, Pompeu Fabra University19, University of Coimbra20, Vrije Universiteit Brussel21, Bethel University22, Laval University23, Hiroshima University24, Medical University of South Carolina25, Hannover Medical School26, Rappaport Faculty of Medicine27, Koç University28, Mahidol University29, University of Helsinki30, Royal Free Hospital31, Fraunhofer Society32, National and Kapodistrian University of Athens33, University of Groningen34, Nippon Medical School35, University of Milan36, Universidad Nacional de Asunción37, Johns Hopkins University38, Hacettepe University39, University of Paris40, University of Mainz41, University of Perugia42, University of Toronto43, University of Copenhagen44, Aarhus University Hospital45, Peking University46
TL;DR: This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) on 3 December 2020 as mentioned in this paper, with the participation of 64 delegates of 50 national and international societies and from 31 countries.
Abstract: This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
223 citations
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TL;DR: In this paper, the authors have produced gene expression profiles of all 302 neurons of the C. elegans nervous system that match the single-cell resolution of its anatomy and wiring diagram, showing that individual neuron classes can be solely identified by combinatorial expression of specific gene families.
212 citations
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TL;DR: This paper conducted a meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.
Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
200 citations
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TL;DR: In this paper, a quantitative health impact assessment for the year 2015 to estimate the effect of air pollution exposure (PM2·5 and NO2) on natural-cause mortality for adult residents (aged ≥20 years) in 969 cities and 47 greater cities in Europe.
195 citations
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TL;DR: Current evidence of AP and PA interactions for health is reviewed and it is suggested that PA behaviour and health effects might be moderated by AP exposure.
154 citations
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TL;DR: The pharmacology, pharmacokinetics, clinical efficacy, and safety of azithromycin in viral infections, with emphasis on COVID-19, are reviewed.
Abstract: SARS-CoV-2 is a novel virus that causes coronavirus disease-19 (COVID-19). Antiviral and immunomodulatory agents have been proposed as potential treatments. Azithromycin exhibits both properties an...
151 citations
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Helmholtz Centre for Environmental Research - UFZ1, Uppsala University2, University of Exeter3, University of Manchester4, Autonomous University of Barcelona5, Goethe University Frankfurt6, University of Salford7, Wageningen University and Research Centre8, Martin Luther University of Halle-Wittenberg9, James Hutton Institute10, Technische Universität München11, Jagiellonian University12, Pompeu Fabra University13, Federal Agency for Nature Conservation14, Bath Spa University15, University of Michigan16
TL;DR: In this paper, the authors present a conceptual framework organizing the pathways linking biodiversity to human health, including reducing harm (e.g., reducing exposure to air and noise pollution), restoring capacities, promoting physical activity, transcendent experiences, and causing harm.
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TL;DR: In this paper, the major long-term pulmonary sequelae in critical patients who survive COVID-19 were evaluated 3 months after hospitalization discharge, and the most frequent symptoms were dyspnea (46.7%), and cough (34.4%).
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University of Auckland1, Beihang University2, Peking University3, Tencent4, University of Erlangen-Nuremberg5, The Chinese University of Hong Kong6, Shenzhen University7, Wuhan University8, Chinese Academy of Sciences9, École Pour l'Informatique et les Techniques Avancées10, Imperial College London11, Shanghai Jiao Tong University12, Fudan University13, French Institute for Research in Computer Science and Automation14, Harbin Institute of Technology15, University of Bologna16, Eindhoven University of Technology17, King's College London18, Information Technology University19, University Hospital Heidelberg20, Leiden University Medical Center21, Pompeu Fabra University22
TL;DR: This large-scale benchmarking study makes a significant step towards much-improved segmentation methods for atrial LGE-MRIs, and will serve as an important benchmark for evaluating and comparing the future works in the field.
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TL;DR: In this paper, the authors calculate years of life lost (YLL) across 81 countries due to COVID-19 attributable deaths, and also conduct an analysis based on estimated excess deaths.
Abstract: Understanding the mortality impact of COVID-19 requires not only counting the dead, but analyzing how premature the deaths are. We calculate years of life lost (YLL) across 81 countries due to COVID-19 attributable deaths, and also conduct an analysis based on estimated excess deaths. We find that over 20.5 million years of life have been lost to COVID-19 globally. As of January 6, 2021, YLL in heavily affected countries are 2-9 times the average seasonal influenza; three quarters of the YLL result from deaths in ages below 75 and almost a third from deaths below 55; and men have lost 45% more life years than women. The results confirm the large mortality impact of COVID-19 among the elderly. They also call for heightened awareness in devising policies that protect vulnerable demographics losing the largest number of life-years.
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TL;DR: In this paper, the results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants were presented, identifying genetic variants associated with DNA methylation at 420,509 DNAm sites in blood.
Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
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TL;DR: The DisGeNET Cytoscape App as mentioned in this paper is a knowledge platform based on a comprehensive catalogue of disease-associated genes and variants, which supports a wide variety of applications through its query and filter functionalities, including the annotation of foreign networks generated by other apps or uploaded by the user.
Abstract: Thanks to the unbiased exploration of genomic variants at large scale, hundreds of thousands of disease-associated loci have been uncovered. In parallel, network-based approaches have proven to be essential to understand the molecular mechanisms underlying human diseases. The use of these approaches has been boosted by the abundance of information about disease associated genes and variants, high quality human interactomics data, and the emergence of new types of omics data. The DisGeNET Cytoscape App combines the capabilities of Cytoscape with those of DisGeNET, a knowledge platform based on a comprehensive catalogue of disease-associated genes and variants. The DisGeNET Cytoscape App contains functions to query, analyze, and visualize different network representations of the gene-disease and variant-disease associations available in DisGeNET. It supports a wide variety of applications through its query and filter functionalities, including the annotation of foreign networks generated by other apps or uploaded by the user. The new release of the DisGeNET Cytoscape App has been designed to support Cytoscape 3.x and incorporates novel distinctive features such as visualization and analysis of variant-disease networks, disease enrichment analysis for genes and variants, and analytic support through Cytoscape Automation. Moreover, the DisGeNET Cytoscape App features an API to access its core functionalities via the REST protocol fostering the development of reproducible and scalable analysis workflows based on DisGeNET data.
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TL;DR: Workers reporting pre-pandemic lifetime mental disorders, those frequently exposed to COVID-19 patients, infected or quarantined/isolated, female workers, and auxiliary nurses should be considered groups in need of mental health monitoring and support.
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TL;DR: The authors in this paper evaluated GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP, and found that GFAP magnitude changes were consistently higher among individuals in symptomatic stages of the AD continuum.
Abstract: Importance Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP. Objective To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP. Design, Setting, and Participants This observational, cross-sectional study collected data from July 29, 2014, to January 31, 2020, from 3 centers. The Translational Biomarkers in Aging and Dementia (TRIAD) cohort (Montreal, Canada) included individuals in the entire AD continuum. Results were confirmed in the Alzheimer’s and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisiere cohort (Paris, France), which included individuals with symptomatic AD. Main Outcomes and Measures Plasma and CSF GFAP levels measured with a Simoa assay were the main outcome. Other measurements included levels of CSF amyloid-β 42/40 (Aβ42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like protein 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and levels of plasma p-tau181 and NfL. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD. Results A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisiere participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL). Plasma GFAP levels were also higher among individuals in symptomatic stages of the AD continuum (TRIAD: CU Aβ-positive mean [SD], 285.0 [142.6] pg/mL, mild cognitive impairment [MCI] Aβ-positive mean [SD], 332.5 [153.6] pg/mL; AD mean [SD], 388.1 [152.8] pg/mL vs CU Aβ-negative mean [SD], 185.1 [93.5] pg/mL; Paris: MCI Aβ-positive, mean [SD], 368.6 [158.5] pg/mL; AD dementia, mean [SD], 376.4 [179.6] pg/mL vs CU Aβ-negative mean [SD], 161.2 [67.1] pg/mL). Plasma GFAP magnitude changes were consistently higher than those of CSF GFAP. Plasma GFAP more accurately discriminated Aβ-positive from Aβ-negative individuals than CSF GFAP (area under the curve for plasma GFAP, 0.69-0.86; area under the curve for CSF GFAP, 0.59-0.76). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant Aβ pathology. Conclusions and Relevance This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD.
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Aarhus University Hospital1, Aarhus University2, Curie Institute3, University of Copenhagen4, Aalborg University5, University of Erlangen-Nuremberg6, University of Jena7, Lund University8, Technische Universität München9, Northwestern University10, University of Belgrade11, University of Birmingham12, University of Leeds13, Pennsylvania State University14, Uppsala University15, Erasmus University Medical Center16, University of Hamburg17, Pompeu Fabra University18
Abstract: The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
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TL;DR: In this article, the authors identify several of the primary factors behind the vulnerability of tourism to COVID-19 (tourism dependency, market structure, the supply of rural accommodation, and health incidence of the pandemic).
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TL;DR: In this paper, the authors show that pseudouridine (Ψ) and 2′-O-methylation (Nm) also result in characteristic base-calling "error" signatures in the nanopore data.
Abstract: Nanopore RNA sequencing shows promise as a method for discriminating and identifying different RNA modifications in native RNA. Expanding on the ability of nanopore sequencing to detect N6-methyladenosine, we show that other modifications, in particular pseudouridine (Ψ) and 2′-O-methylation (Nm), also result in characteristic base-calling ‘error’ signatures in the nanopore data. Focusing on Ψ modification sites, we detected known and uncovered previously unreported Ψ sites in mRNAs, non-coding RNAs and rRNAs, including a Pus4-dependent Ψ modification in yeast mitochondrial rRNA. To explore the dynamics of pseudouridylation, we treated yeast cells with oxidative, cold and heat stresses and detected heat-sensitive Ψ-modified sites in small nuclear RNAs, small nucleolar RNAs and mRNAs. Finally, we developed a software, nanoRMS, that estimates per-site modification stoichiometries by identifying single-molecule reads with altered current intensity and trace profiles. This work demonstrates that Nm and Ψ RNA modifications can be detected in cellular RNAs and that their modification stoichiometry can be quantified by nanopore sequencing of native RNA. Nanopore sequencing detects pseudouridine and 2′-O-methylation modifications in cellular RNAs.
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University of Vienna1, University of Exeter2, Jagiellonian University3, Estonian University of Life Sciences4, University of Washington5, Pompeu Fabra University6, ISCTE – University Institute of Lisbon7, Karolinska Institutet8, Griffith University9, California State University San Marcos10, University of British Columbia11
TL;DR: In this article, the authors explored associations between multiple measures of mental health (positive well-being, mental distress, depression/anxiety medication use) and exposures (residential/recreational visits) to different natural settings (green/inland-blue/coastal-blue spaces); and nature connectedness, across season and country.
Abstract: Living near, recreating in, and feeling psychologically connected to, the natural world are all associated with better mental health, but many exposure-related questions remain. Using data from an 18-country survey (n = 16,307) we explored associations between multiple measures of mental health (positive well-being, mental distress, depression/anxiety medication use) and: (a) exposures (residential/recreational visits) to different natural settings (green/inland-blue/coastal-blue spaces); and (b) nature connectedness, across season and country. People who lived in greener/coastal neighbourhoods reported higher positive well-being, but this association largely disappeared when recreational visits were controlled for. Frequency of recreational visits to green, inland-blue, and coastal-blue spaces in the last 4 weeks were all positively associated with positive well-being and negatively associated with mental distress. Associations with green space visits were relatively consistent across seasons and countries but associations with blue space visits showed greater heterogeneity. Nature connectedness was also positively associated with positive well-being and negatively associated with mental distress and was, along with green space visits, associated with a lower likelihood of using medication for depression. By contrast inland-blue space visits were associated with a greater likelihood of using anxiety medication. Results highlight the benefits of multi-exposure, multi-response, multi-country studies in exploring complexity in nature-health associations.
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TL;DR: It is shown that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans.
Abstract: The clinical applicability of porcine xenotransplantation-a long-investigated alternative to the scarce availability of human organs for patients with organ failure-is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated PERVs. Here, using a combination of CRISPR-Cas9 and transposon technologies, we show that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans. The engineered pigs exhibit normal physiology, fertility and germline transmission of the 13 genes and 42 alleles edited. Using in vitro assays, we show that cells from the engineered pigs are resistant to human humoral rejection, cell-mediated damage and pathogenesis associated with dysregulated coagulation. The extensive genome engineering of pigs for greater compatibility with the human immune system may eventually enable safe and effective porcine xenotransplantation.
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TL;DR: This work introduces a low-complexity beam squint mitigation scheme based on true-time-delay and proposes a novel variant of the popular orthogonal matching pursuit (OMP) algorithm to accurately estimate the channel with low training overhead.
Abstract: Terahertz (THz) communication is widely considered as a key enabler for future 6G wireless systems. However, THz links are subject to high propagation losses and inter-symbol interference due to the frequency selectivity of the channel. Massive multiple-input multiple-output (MIMO) along with orthogonal frequency division multiplexing (OFDM) can be used to deal with these problems. Nevertheless, when the propagation delay across the base station (BS) antenna array exceeds the symbol period, the spatial response of the BS array varies over the OFDM subcarriers. This phenomenon, known as beam squint, renders narrowband combining approaches ineffective. Additionally, channel estimation becomes challenging in the absence of combining gain during the training stage. In this work, we address the channel estimation and hybrid combining problems in wideband THz massive MIMO with uniform planar arrays. Specifically, we first introduce a low-complexity beam squint mitigation scheme based on true-time-delay. Next, we propose a novel variant of the popular orthogonal matching pursuit (OMP) algorithm to accurately estimate the channel with low training overhead. Our channel estimation and hybrid combining schemes are analyzed both theoretically and numerically. Moreover, the proposed schemes are extended to the multi-antenna user case. Simulation results are provided showcasing the performance gains offered by our design compared to standard narrowband combining and OMP-based channel estimation.
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University of Antwerp1, Université libre de Bruxelles2, University of Oldenburg3, Maastricht University4, World Health Organization5, Vrije Universiteit Brussel6, Jagiellonian University Medical College7, University Medical Center Groningen8, Hanze University of Applied Sciences9, Medical University of Białystok10, Catholic University of the Sacred Heart11, Autonomous University of Barcelona12, Pompeu Fabra University13
TL;DR: In this article, a systematic search was performed in Medline, SCOPUS and Web of Sciences looking for all articles describing the use of ultrasound in the assessment of muscle not described in the first recommendations, published from 1/1/2018 until 31/01/2020.
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University of Oxford1, Flemish Institute for Technological Research2, University of Hasselt3, Imperial College London4, Drexel University5, Pompeu Fabra University6, Dresden University of Technology7, University of Oregon8, University of Zurich9, World Health Organization10, Austrian Federal Railways11, Colorado State University12, University of Natural Resources and Life Sciences, Vienna13
TL;DR: In this paper, the authors collected travel activity data in seven European cities and derived life cycle CO2 emissions across modes and purposes, with car travel contributing 70% and cycling 1%.
Abstract: Active travel (walking or cycling for transport) is considered the most sustainable form of personal transport. Yet its net effects on mobility-related CO2 emissions are complex and under-researched. Here we collected travel activity data in seven European cities and derived life cycle CO2 emissions across modes and purposes. Daily mobility-related life cycle CO2 emissions were 3.2 kgCO2 per person, with car travel contributing 70% and cycling 1%. Cyclists had 84% lower life cycle CO2 emissions than non-cyclists. Life cycle CO2 emissions decreased by −14% per additional cycling trip and decreased by −62% for each avoided car trip. An average person who ‘shifted travel modes’ from car to bike decreased life cycle CO2 emissions by 3.2 kgCO2/day. Promoting active travel should be a cornerstone of strategies to meet net zero carbon targets, particularly in urban areas, while also improving public health and quality of urban life.
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TL;DR: The importance of NMD for gene editing and tumor evolution, and how inhibiting NMD may be an effective strategy to increase the efficacy of cancer immunotherapy are discussed.
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TL;DR: In this article, the prevalence of current depressive disorder in 27 European countries and by gender was estimated using the Patient Health Questionnaire (PHQ-8), with depressive disorder defined as a score of 10 or higher, and the overall prevalence was 6.38% (95% CI 6·24-6·52) with important variation across countries, ranging from 2·58% (2·14-3·02) in the Czech Republic to 10·33% (9·33-11·32) in Iceland.
Abstract: Summary Background We aimed to estimate the prevalence of current depressive disorder in 27 European countries, and to explore differences in prevalence between European countries and by gender. Methods In this population-based study, we analysed data from respondents living in 27 European countries who were included in the second wave of the European Health Interview Survey, collected between 2013 and 2015. We assessed the prevalence of current depressive disorder using the eight-item Patient Health Questionnaire (PHQ-8), with depressive disorder defined as a PHQ-8 score of 10 or higher. Prevalence estimates and 95% CIs were calculated for all 27 countries overall and for each country individually. We assessed variation in prevalence (country vs the rest of Europe) using crude and adjusted prevalence ratios obtained from negative binomial regression models. We did all analyses for the total sample and stratified by gender. Findings Our analysis sample comprised 258 888 individuals, of whom 117 310 (weighted proportion 47·8%) were men and 141 578 (52·2%) were women. The overall prevalence of current depressive disorder was 6·38% (95% CI 6·24–6·52) with important variation across countries, ranging from 2·58% (2·14–3·02) in the Czech Republic to 10·33% (9·33–11·32) in Iceland. Prevalence was higher in women (7·74% [7·53–7·95]) than in men (4·89% [4·71–5·08]), with clear gender differences for all countries except Finland and Croatia. Compared with the other European countries in our sample, those with the highest adjusted prevalence ratios were Germany (1·80 [1·71–1·89]) and Luxembourg (1·50 [1·35–1·66]), and those with the lowest adjusted prevalence ratios were Slovakia (0·28 [0·24–0·33]) and the Czech Republic (0·32 [0·27–0·38]). Interpretation Depressive disorders, although common across Europe, vary substantially in prevalence between countries. These results could be a baseline for monitoring the prevalence of current depressive disorder both at a country level in Europe and for planning health-care resources and services. Funding UK Medical Research Council and CIBER Epidemiology and Public Health (CIBERESP).
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TL;DR: In this article, the authors estimate the number of premature deaths among adult residents that could be prevented in cities in 31 European countries, if the WHO recommendation for universal access to green space was achieved.
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TL;DR: The role and regulation of satellite cells in skeletal muscle homeostasis and regeneration is discussed in this paper, highlighting the cell-intrinsic control of quiescence versus activation, the importance of satellite cell-niche communication, and deregulation of these mechanisms associated with ageing.
Abstract: Skeletal muscle contains a designated population of adult stem cells, called satellite cells, which are generally quiescent. In homeostasis, satellite cells proliferate only sporadically and usually by asymmetric cell division to replace myofibres damaged by daily activity and maintain the stem cell pool. However, satellite cells can also be robustly activated upon tissue injury, after which they undergo symmetric divisions to generate new stem cells and numerous proliferating myoblasts that later differentiate to muscle cells (myocytes) to rebuild the muscle fibre, thereby supporting skeletal muscle regeneration. Recent discoveries show that satellite cells have a great degree of population heterogeneity, and that their cell fate choices during the regeneration process are dictated by both intrinsic and extrinsic mechanisms. Extrinsic cues come largely from communication with the numerous distinct stromal cell types in their niche, creating a dynamically interactive microenvironment. This Review discusses the role and regulation of satellite cells in skeletal muscle homeostasis and regeneration. In particular, we highlight the cell-intrinsic control of quiescence versus activation, the importance of satellite cell–niche communication, and deregulation of these mechanisms associated with ageing. The increasing understanding of how satellite cells are regulated will help to advance muscle regeneration and rejuvenation therapies. Satellite cells are skeletal muscle stem cells that are largely quiescent. They are activated upon muscle damage and differentiate into muscle cells or return to quiescence. These processes are controlled by cell-intrinsic mechanisms and by signals from the niche, and are deregulated in ageing, leading to impaired muscle regeneration.