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Showing papers by "University of Bergen published in 2018"


Journal ArticleDOI
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4  +414 moreInstitutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

5,988 citations


Journal ArticleDOI
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4  +1025 moreInstitutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).

5,211 citations


Journal ArticleDOI
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1  +1050 moreInstitutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.

2,910 citations


Journal ArticleDOI
David Capper1, David Capper2, David Capper3, David T.W. Jones2  +168 moreInstitutions (54)
22 Mar 2018-Nature
TL;DR: This work presents a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and shows that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

1,620 citations



Journal ArticleDOI
22 Jun 2018-Science
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

1,357 citations


Journal ArticleDOI
TL;DR: The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome and this update comes with a new web framework with an interactive and responsive user-interface, along with new features.
Abstract: JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition, we have introduced 316 TFFMs (95 for vertebrates, 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally, this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package.

1,282 citations


Journal ArticleDOI
Antonio F. Pardiñas1, Peter Holmans1, Andrew Pocklington1, Valentina Escott-Price1, Stephan Ripke2, Stephan Ripke3, Noa Carrera1, Sophie E. Legge1, Sophie Bishop1, D. F. Cameron1, Marian L. Hamshere1, Jun Han1, Leon Hubbard1, Amy Lynham1, Kiran Kumar Mantripragada1, Elliott Rees1, James H. MacCabe4, Steven A. McCarroll5, Bernhard T. Baune6, Gerome Breen7, Gerome Breen4, Enda M. Byrne8, Udo Dannlowski9, Thalia C. Eley4, Caroline Hayward10, Nicholas G. Martin8, Nicholas G. Martin11, Andrew M. McIntosh10, Robert Plomin4, David J. Porteous10, Naomi R. Wray8, Armando Caballero12, Daniel H. Geschwind13, Laura M. Huckins14, Douglas M. Ruderfer14, Enrique Santiago15, Pamela Sklar14, Eli A. Stahl14, Hyejung Won13, Esben Agerbo16, Esben Agerbo17, Thomas Damm Als17, Thomas Damm Als16, Ole A. Andreassen18, Ole A. Andreassen19, Marie Bækvad-Hansen17, Marie Bækvad-Hansen20, Preben Bo Mortensen17, Preben Bo Mortensen16, Carsten Bøcker Pedersen16, Carsten Bøcker Pedersen17, Anders D. Børglum17, Anders D. Børglum16, Jonas Bybjerg-Grauholm20, Jonas Bybjerg-Grauholm17, Srdjan Djurovic18, Srdjan Djurovic21, Naser Durmishi, Marianne Giørtz Pedersen17, Marianne Giørtz Pedersen16, Vera Golimbet, Jakob Grove, David M. Hougaard20, David M. Hougaard17, Manuel Mattheisen17, Manuel Mattheisen16, Espen Molden, Ole Mors17, Ole Mors22, Merete Nordentoft23, Merete Nordentoft17, Milica Pejovic-Milovancevic24, Engilbert Sigurdsson, Teimuraz Silagadze25, Christine Søholm Hansen17, Christine Søholm Hansen20, Kari Stefansson26, Hreinn Stefansson26, Stacy Steinberg26, Sarah Tosato27, Thomas Werge28, Thomas Werge17, Thomas Werge23, David A. Collier29, David A. Collier4, Dan Rujescu30, Dan Rujescu31, George Kirov1, Michael J. Owen1, Michael Conlon O'Donovan1, James T.R. Walters1 
TL;DR: A new genome-wide association study of schizophrenia is reported, and through meta-analysis with existing data and integrating genomic fine-mapping with brain expression and chromosome conformation data, 50 novel associated loci and 145 loci are identified.
Abstract: Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.

1,259 citations


Journal ArticleDOI
Anubha Mahajan1, Daniel Taliun2, Matthias Thurner1, Neil R. Robertson1, Jason M. Torres1, N. William Rayner3, N. William Rayner1, Anthony Payne1, Valgerdur Steinthorsdottir4, Robert A. Scott5, Niels Grarup6, James P. Cook7, Ellen M. Schmidt2, Matthias Wuttke8, Chloé Sarnowski9, Reedik Mägi10, Jana Nano11, Christian Gieger, Stella Trompet12, Cécile Lecoeur13, Michael Preuss14, Bram P. Prins3, Xiuqing Guo15, Lawrence F. Bielak2, Jennifer E. Below16, Donald W. Bowden17, John C. Chambers, Young-Jin Kim, Maggie C.Y. Ng17, Lauren E. Petty16, Xueling Sim18, Weihua Zhang19, Weihua Zhang20, Amanda J. Bennett1, Jette Bork-Jensen6, Chad M. Brummett2, Mickaël Canouil13, Kai-Uwe Ec Kardt21, Krista Fischer10, Sharon L.R. Kardia2, Florian Kronenberg22, Kristi Läll10, Ching-Ti Liu9, Adam E. Locke23, Jian'an Luan5, Ioanna Ntalla24, Vibe Nylander1, Sebastian Schönherr22, Claudia Schurmann14, Loic Yengo13, Erwin P. Bottinger14, Ivan Brandslund25, Cramer Christensen, George Dedoussis26, Jose C. Florez, Ian Ford27, Oscar H. Franco11, Timothy M. Frayling28, Vilmantas Giedraitis29, Sophie Hackinger3, Andrew T. Hattersley28, Christian Herder30, M. Arfan Ikram11, Martin Ingelsson29, Marit E. Jørgensen31, Marit E. Jørgensen25, Torben Jørgensen32, Torben Jørgensen6, Jennifer Kriebel, Johanna Kuusisto33, Symen Ligthart11, Cecilia M. Lindgren34, Cecilia M. Lindgren1, Allan Linneberg35, Allan Linneberg6, Valeriya Lyssenko36, Valeriya Lyssenko37, Vasiliki Mamakou26, Thomas Meitinger38, Karen L. Mohlke39, Andrew D. Morris40, Andrew D. Morris41, Girish N. Nadkarni14, James S. Pankow42, Annette Peters, Naveed Sattar43, Alena Stančáková33, Konstantin Strauch44, Kent D. Taylor15, Barbara Thorand, Gudmar Thorleifsson4, Unnur Thorsteinsdottir45, Unnur Thorsteinsdottir4, Jaakko Tuomilehto, Daniel R. Witte46, Josée Dupuis9, Patricia A. Peyser2, Eleftheria Zeggini3, Ruth J. F. Loos14, Philippe Froguel20, Philippe Froguel13, Erik Ingelsson47, Erik Ingelsson48, Lars Lind29, Leif Groop49, Leif Groop37, Markku Laakso33, Francis S. Collins50, J. Wouter Jukema12, Colin N. A. Palmer51, Harald Grallert, Andres Metspalu10, Abbas Dehghan20, Abbas Dehghan11, Anna Köttgen8, Gonçalo R. Abecasis2, James B. Meigs52, Jerome I. Rotter15, Jonathan Marchini1, Oluf Pedersen6, Torben Hansen25, Torben Hansen6, Claudia Langenberg5, Nicholas J. Wareham5, Kari Stefansson45, Kari Stefansson4, Anna L. Gloyn1, Andrew P. Morris7, Andrew P. Morris10, Andrew P. Morris1, Michael Boehnke2, Mark I. McCarthy1 
TL;DR: Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

1,136 citations


Book
29 May 2018
TL;DR: A.M. Andersen and M.J. Marais Appendix - Checklist for Isoflavonoids O.C. Williams C-Glycosylflavonoids.
Abstract: Separation and Quantification of Flavonoids A. Marston and K. Hostettmann Spectroscopic Techniques Applied to Flavonoids T. Fossen and O.M. Andersen Molecular Biology and Biotechnology of Flavonoid Biosynthesis K.M. Davies and K.E. Schwinn Flavonoids in Foods J.A.M. Kyle and G.G. Duthie Flavonoids in Wine V. Cheynier Dietary Flavonoids and Health - Broadening the Perspective M. Clifford and J.E. Brown Isoflavonoids and Human Health H. Wiseman Flavonoid Functions in Plants K.S. Gould and C. Lister Flavonoid-Protein Interactions O. Dangles and C. Dufour The Anthocyanins O.M. Andersen and M.Jordheim Flavans and Proanthocyanidins D. Ferreira, D. Slade, and J.P.J. Marais Flavones and Flavonols K.M. Valant-Vetschera and E. Wollenweber Flavone and Flavonol O-Glycosides C.A. Williams C-Glycosylflavonoids M. Jay, M.R. Viricel, and J.F. Gonnet Flavanones and Dihydroflavonols R.J. Grayer and N.C. Veitch Chalcones, Dihydrochalcones, and Aurones N.C. Veitch and R.J. Grayer Bi-, Tri-, Tetra-, Penta-, and Hexaflavonoids D. Ferreira, D. Slade, and J.P.J. Marais Appendix - Checklist for Isoflavonoids O.M. Andersen Index

1,068 citations


Journal ArticleDOI
TL;DR: In this article, the authors provide a short overview of recent advances and some associated challenges in machine learning applied to medical image processing and image analysis, and provide a starting point for people interested in experimenting and perhaps contributing to the field of machine learning for medical imaging.
Abstract: What has happened in machine learning lately, and what does it mean for the future of medical image analysis? Machine learning has witnessed a tremendous amount of attention over the last few years. The current boom started around 2009 when so-called deep artificial neural networks began outperforming other established models on a number of important benchmarks. Deep neural networks are now the state-of-the-art machine learning models across a variety of areas, from image analysis to natural language processing, and widely deployed in academia and industry. These developments have a huge potential for medical imaging technology, medical data analysis, medical diagnostics and healthcare in general, slowly being realized. We provide a short overview of recent advances and some associated challenges in machine learning applied to medical image processing and image analysis. As this has become a very broad and fast expanding field we will not survey the entire landscape of applications, but put particular focus on deep learning in MRI. Our aim is threefold: (i) give a brief introduction to deep learning with pointers to core references; (ii) indicate how deep learning has been applied to the entire MRI processing chain, from acquisition to image retrieval, from segmentation to disease prediction; (iii) provide a starting point for people interested in experimenting and perhaps contributing to the field of machine learning for medical imaging by pointing out good educational resources, state-of-the-art open-source code, and interesting sources of data and problems related medical imaging.

Journal ArticleDOI
Jeanne E. Savage1, Philip R. Jansen2, Philip R. Jansen1, Sven Stringer1, Kyoko Watanabe1, Julien Bryois3, Christiaan de Leeuw1, Mats Nagel, Swapnil Awasthi4, Peter B. Barr5, Jonathan R. I. Coleman6, Katrina L. Grasby7, Anke R. Hammerschlag1, Jakob Kaminski4, Robert Karlsson3, Eva Krapohl8, Max Lam, Marianne Nygaard9, Chandra A. Reynolds10, Joey W. Trampush11, Hannah Young12, Delilah Zabaneh8, Sara Hägg3, Narelle K. Hansell13, Ida K. Karlsson3, Sten Linnarsson3, Grant W. Montgomery13, Grant W. Montgomery7, Ana B. Muñoz-Manchado3, Erin Burke Quinlan8, Gunter Schumann8, Nathan G. Skene14, Nathan G. Skene3, Bradley T. Webb5, Tonya White2, Dan E. Arking15, Dimitrios Avramopoulos15, Robert M. Bilder16, Panos Bitsios17, Katherine E. Burdick18, Katherine E. Burdick19, Katherine E. Burdick20, Tyrone D. Cannon21, Ornit Chiba-Falek, Andrea Christoforou22, Elizabeth T. Cirulli, Eliza Congdon16, Aiden Corvin23, Gail Davies24, Ian J. Deary24, Pamela DeRosse25, Pamela DeRosse26, Dwight Dickinson27, Srdjan Djurovic28, Srdjan Djurovic29, Gary Donohoe30, Emily Drabant Conley, Johan G. Eriksson31, Thomas Espeseth32, Nelson A. Freimer16, Stella G. Giakoumaki17, Ina Giegling33, Michael Gill23, David C. Glahn21, Ahmad R. Hariri34, Alex Hatzimanolis35, Alex Hatzimanolis36, Matthew C. Keller37, Emma Knowles21, Deborah C. Koltai34, Bettina Konte33, Jari Lahti31, Stephanie Le Hellard29, Todd Lencz26, Todd Lencz25, David C. Liewald24, Edythe D. London16, Astri J. Lundervold29, Anil K. Malhotra25, Anil K. Malhotra26, Ingrid Melle32, Ingrid Melle29, Derek W. Morris30, Anna C. Need38, William Ollier39, Aarno Palotie31, Aarno Palotie18, Aarno Palotie40, Antony Payton39, Neil Pendleton41, Russell A. Poldrack42, Katri Räikkönen31, Ivar Reinvang32, Panos Roussos20, Panos Roussos19, Dan Rujescu33, Fred W. Sabb43, Matthew A. Scult34, Olav B. Smeland32, Nikolaos Smyrnis36, Nikolaos Smyrnis35, John M. Starr24, Vidar M. Steen29, Nikos C. Stefanis35, Nikos C. Stefanis36, Richard E. Straub15, Kjetil Sundet32, Henning Tiemeier2, Aristotle N. Voineskos44, Daniel R. Weinberger15, Elisabeth Widen31, Jin Yu, Gonçalo R. Abecasis45, Ole A. Andreassen32, Gerome Breen6, Lene Christiansen9, Birgit Debrabant9, Danielle M. Dick5, Andreas Heinz4, Jens Hjerling-Leffler3, M. Arfan Ikram46, Kenneth S. Kendler5, Nicholas G. Martin7, Sarah E. Medland7, Nancy L. Pedersen3, Robert Plomin8, Tinca J. C. Polderman1, Stephan Ripke4, Stephan Ripke47, Stephan Ripke18, Sophie van der Sluis, Patrick Sullivan3, Patrick Sullivan48, Scott I. Vrieze12, Margaret J. Wright13, Danielle Posthuma1 
TL;DR: A large-scale genetic association study of intelligence identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure, a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.


Journal ArticleDOI
TL;DR: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.
Abstract: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

Journal ArticleDOI
Douglas M. Ruderfer1, Stephan Ripke2, Stephan Ripke3, Stephan Ripke4  +628 moreInstitutions (156)
14 Jun 2018-Cell
TL;DR: For the first time, specific loci that distinguish between BD and SCZ are discovered and polygenic components underlying multiple symptom dimensions are identified that point to the utility of genetics to inform symptomology and potential treatment.

Journal ArticleDOI
04 Apr 2018-Nature
TL;DR: Analysis of changes in plant species richness on mountain summits over the past 145 years suggests that increased climatic warming has led to an acceleration in species richness increase, strikingly synchronized with accelerated global warming.
Abstract: Globally accelerating trends in societal development and human environmental impacts since the mid-twentieth century 1–7 are known as the Great Acceleration and have been discussed as a key indicator of the onset of the Anthropocene epoch 6 . While reports on ecological responses (for example, changes in species range or local extinctions) to the Great Acceleration are multiplying 8, 9 , it is unknown whether such biotic responses are undergoing a similar acceleration over time. This knowledge gap stems from the limited availability of time series data on biodiversity changes across large temporal and geographical extents. Here we use a dataset of repeated plant surveys from 302 mountain summits across Europe, spanning 145 years of observation, to assess the temporal trajectory of mountain biodiversity changes as a globally coherent imprint of the Anthropocene. We find a continent-wide acceleration in the rate of increase in plant species richness, with five times as much species enrichment between 2007 and 2016 as fifty years ago, between 1957 and 1966. This acceleration is strikingly synchronized with accelerated global warming and is not linked to alternative global change drivers. The accelerating increases in species richness on mountain summits across this broad spatial extent demonstrate that acceleration in climate-induced biotic change is occurring even in remote places on Earth, with potentially far-ranging consequences not only for biodiversity, but also for ecosystem functioning and services.

Journal ArticleDOI
Gail Davies1, Max Lam, Sarah E. Harris1, Joey W. Trampush2  +254 moreInstitutions (79)
TL;DR: In this paper, the authors combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci associated with general cognitive function.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Journal ArticleDOI
TL;DR: A review of relevant studies and recent progress on four levels introduces different types of biomedical materials, and discusses existing problems and development issues with 3D printing that are related to materials and to the construction of extracellular matrix in vitro for medical applications.

Journal ArticleDOI
Morad Aaboud1, Georges Aad2, Brad Abbott3, Ovsat Abdinov4  +2954 moreInstitutions (225)
TL;DR: In this paper, a search for new phenomena in final states with an energetic jet and large missing transverse momentum is reported, and the results are translated into exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, and supersymmetric particles in several compressed scenarios.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses proton-proton collision data corresponding to an integrated luminosity of 36.1 fb−1 at a centre-of-mass energy of 13 TeV collected in 2015 and 2016 with the ATLAS detector at the Large Hadron Collider. Events are required to have at least one jet with a transverse momentum above 250 GeV and no leptons (e or μ). Several signal regions are considered with increasing requirements on the missing transverse momentum above 250 GeV. Good agreement is observed between the number of events in data and Standard Model predictions. The results are translated into exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, and supersymmetric particles in several compressed scenarios.

Journal ArticleDOI
TL;DR: This review provides an overview of eukaryotic N-terminal acetyltransferases (NATs) and the impact of Nt-acetylation, and discusses other functions of known NATs and outline methods for studying NT- acetylation.
Abstract: N-terminal acetylation (Nt-acetylation) is a widespread protein modification among eukaryotes and prokaryotes alike By appending an acetyl group to the N-terminal amino group, the charge, hydrophobicity, and size of the N-terminus is altered in an irreversible manner This alteration has implications for the lifespan, folding characteristics and binding properties of the acetylated protein The enzymatic machinery responsible for Nt-acetylation has been largely described, but significant knowledge gaps remain In this review, we provide an overview of eukaryotic N-terminal acetyltransferases (NATs) and the impact of Nt-acetylation We also discuss other functions of known NATs and outline methods for studying Nt-acetylation

Journal ArticleDOI
18 Dec 2018-eLife
TL;DR: It is concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO), and it is reported that intrastriatal injections suppress glymphatic function.
Abstract: The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.

Journal ArticleDOI
TL;DR: In this article, the authors integrate multiple datasets to assess the relationships between species richness in mountains, geology and climate at global and regional scales, and find that centres of species richness correlate with areas of high temperatures, annual rainfall and topographic relief, supporting previous studies.
Abstract: Mountains are key features of the Earth’s surface and host a substantial proportion of the world’s species. However, the links between the evolution and distribution of biodiversity and the formation of mountains remain poorly understood. Here, we integrate multiple datasets to assess the relationships between species richness in mountains, geology and climate at global and regional scales. Specifically, we analyse how erosion, relief, soil and climate relate to the geographical distribution of terrestrial tetrapods, which include amphibians, birds and mammals. We find that centres of species richness correlate with areas of high temperatures, annual rainfall and topographic relief, supporting previous studies. We unveil additional links between mountain-building processes and biodiversity: species richness correlates with erosion rates and heterogeneity of soil types, with a varying response across continents. These additional links are prominent but under-explored, and probably relate to the interplay between surface uplift, climate change and atmospheric circulation through time. They are also influenced by the location and orientation of mountain ranges in relation to air circulation patterns, and how species diversification, dispersal and refugia respond to climate change. A better understanding of biosphere–lithosphere interactions is needed to understand the patterns and evolution of mountain biodiversity across space and time.

Journal ArticleDOI
TL;DR: It is postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk.

Journal ArticleDOI
Brad Abbott1, Allan G Clark2, S. Latorre, O. Crespo-Lopez3  +397 moreInstitutions (51)
TL;DR: The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown.
Abstract: During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector.

Journal ArticleDOI
TL;DR: In this article, the authors propose a meta-theoretical framework for analyzing national energy transitions by considering three types of systems: energy flows and markets, energy technologies, and energy-related policies.
Abstract: Economic development, technological innovation, and policy change are especially prominent factors shaping energy transitions. Therefore explaining energy transitions requires combining insights from disciplines investigating these factors. The existing literature is not consistent in identifying these disciplines nor proposing how they can be combined. We conceptualize national energy transitions as a co-evolution of three types of systems: energy flows and markets, energy technologies, and energy-related policies. The focus on the three types of systems gives rise to three perspectives on national energy transitions: techno-economic with its roots in energy systems analysis and various domains of economics; socio-technical with its roots in sociology of technology, STS, and evolutionary economics; and political with its roots in political science. We use the three perspectives as an organizing principle to propose a meta-theoretical framework for analyzing national energy transitions. Following Elinor Ostrom's approach, the proposed framework explains national energy transitions through a nested conceptual map of variables and theories. In comparison with the existing meta-theoretical literature, the three perspectives framework elevates the role of political science since policies are likely to be increasingly prominent in shaping 21st century energy transitions.

Journal ArticleDOI
Rafael Lozano1, Nancy Fullman, Degu Abate2, Solomon M Abay  +1313 moreInstitutions (252)
TL;DR: A global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends and a estimates of health-related SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous.

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TL;DR: This article reviews recent discoveries as well as approaches to the care of affected patients in autoimmune polyendocrine syndromes.
Abstract: Autoimmune Polyendocrine Syndromes Autoimmune polyendocrine syndromes comprise a diverse group of clinical entities involving functional impairment of multiple endocrine glands due to loss of immune tolerance. This article reviews recent discoveries as well as approaches to the care of affected patients.

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TL;DR: It is argued that the chronology and physical diversity of Pleistocene human fossils and the African archaeological record support an emerging view of a highly structured African prehistory that should be considered in human evolutionary inferences, prompting new interpretations, questions, and interdisciplinary research directions.
Abstract: We challenge the view that our species, Homo sapiens, evolved within a single population and/or region of Africa. The chronology and physical diversity of Pleistocene human fossils suggest that morphologically varied populations pertaining to the H. sapiens clade lived throughout Africa. Similarly, the African archaeological record demonstrates the polycentric origin and persistence of regionally distinct Pleistocene material culture in a variety of paleoecological settings. Genetic studies also indicate that present-day population structure within Africa extends to deep times, paralleling a paleoenvironmental record of shifting and fractured habitable zones. We argue that these fields support an emerging view of a highly structured African prehistory that should be considered in human evolutionary inferences, prompting new interpretations, questions, and interdisciplinary research directions.


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TL;DR: Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety, and relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a substantial number of new cases of depression.
Abstract: Objective:The purpose of the present study was to address 1) whether exercise provides protection against new-onset depression and anxiety and 2) if so, the intensity and amount of exercise required to gain protection and, lastly, 3) the mechanisms that underlie any association.Method:A “healthy” cohort of 33,908 adults, selected on the basis of having no symptoms of common mental disorder or limiting physical health conditions, was prospectively followed for 11 years. Validated measures of exercise, depression, anxiety, and a range of potential confounding and mediating factors were collected.Results:Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety. The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity. After adjustment for confounders, the population attributable fraction suggests that, assuming the relationship is causal, 12% of future cases of depression could have been prev...