| 1. |
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| 2. |
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| 3. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 4. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)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 scale1–3. 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 genomes8,10–18.
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| 5. |
- Stroth, U., et al.
(author)
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Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
-
Journal article (peer-reviewed)abstract
- An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts.
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| 6. |
- Crous, P. W., et al.
(author)
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Fungal Planet description sheets: 1182-1283
- 2021
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In: Persoonia. - : Naturalis Biodiversity Center. - 0031-5850. ; 46, s. 313-528
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Algeria, Phaeoacremonium adelophialidum from Vitis vinifera. Antarctica, Comoclathris antarctica from soil. Australia, Coniochaeta salicifolia as endophyte from healthy leaves of Geijera salicifolia, Eremothecium peggii in fruit of Citrus australis, Microdochium ratticaudae from stem of Sporobolus natalensis, Neocelosporium corymbiae on stems of Corymbia variegata, Phytophthora kelmanii from rhizosphere soil of Ptilotus pyramidatus, Pseudosydowia backhousiae on living leaves of Backhousia citriodora, Pseudosydowia indooroopillyensis, Pseudosydowia louisecottisiae and Pseudosydowia queenslandica on living leaves of Eucalyptus sp. Brazil, Absidia montepascoalis from soil. Chile, Ilyonectria zarorii from soil under Maytenus boaria. Costa Rica, Colletotrichum filicis from an unidentified fern. Croatia, Mollisia endogranulata on deteriorated hardwood. Czech Republic, Arcopilus navicularis from tea bag with fruit tea, Neosetophoma buxi as endophyte from Buxus sempervirens, Xerochrysium bohemicum on surface of biscuits with chocolate glaze and filled with jam. France, Entoloma cyaneobasale on basic to calcareous soil, Fusarium aconidiale from Triticum aestivum, Fusarium juglandicola from buds of Juglans regia. Germany, Tetraploa endophytica as endophyte from Microthlaspi perfoliatum roots. India, Castanediella ambae on leaves of Mangifera indica, Lactifluus kanadii on soil under Castanopsis sp., Penicillium uttarakhandense from soil. Italy, Penicillium ferraniaense from compost. Namibia, Bezerromyces gobabebensis on leaves of unidentified succulent, Cladosporium stipagrostidicola on leaves of Stipagrostis sp., Cymostachys euphorbiae on leaves of Euphorbia sp., Deniquelata hypolithi from hypolith under a rock, Hysterobrevium walvisbayicola on leaves of unidentified tree, Knufia hypolithi and Knufia walvisbayicola from hypolith under a rock, Lapidomyces stipagrostidicola on leaves of Stipagrostis sp., Nothophaeotheca mirabibensis (incl. Nothophaeotheca gen. nov.) on persistent inflorescence remains of Blepharis obmitrata, Paramyrothecium salvadorae on twigs of Salvadora persica, Preussia procaviicola on dung of Procavia sp., Sordaria equicola on zebra dung, Volutella salvadorae on stems of Salvadora persica. Netherlands, Entoloma ammophilum on sandy soil, Entoloma pseudocruentatum on nutrient poor (acid) soil, Entoloma pudens on plant debris, amongst grasses. New Zealand, Amorocoelophoma neoregeliae from leaf spots of Neoregelia sp., Aquilomyces metrosideri and Septoriella callistemonis from stem discolouration and leaf spots of Metrosideros sp., Cadophora neoregeliae from leaf spots of Neoregelia sp., Flexuomyces asteliae (incl. Flexuomyces gen. nov.) and Mollisia asteliae from leaf spots of Astelia chathamica, Ophioceras freycinetiae from leaf spots of Freycinetia banksii, Phaeosphaeria caricis-sectae from leaf spots of Carex secta. Norway, Cuphophyllus flavipesoides on soil in semi-natural grassland, Entoloma coracis on soil in calcareous Pinus and Tilia forests, Entoloma cyaneolilacinum on soil semi-natural grasslands, Inocybe norvegica on gravelly soil. Pakistan, Butyriboletus parachinarensis on soil in association with Quercus baloot. Poland, Hyalodendriella bialowiezensis on debris beneath fallen bark of Norway spruce Picea abies. Russia, Bolbitius sibiricus on. moss covered rotting trunk of Populus tremula, Crepidotus wasseri on debris of Populus tremula, Entoloma isborscanum on soil on calcareous grasslands, Entoloma subcoracis on soil in subalpine grasslands, Hydropus lecythiocystis on rotted wood of Betula pendula, Meruliopsis faginea on fallen dead branches of Fagus orientalis, Metschnikowia taurica from fruits of Ziziphus jujube, Suillus praetermissus on soil, Teunia lichenophila as endophyte from Cladonia rangiferina. Slovakia, Hygrocybe fulgens on mowed grassland, Pleuroflammula pannonica from corticated branches of Quercus sp. South Africa, Acrodontium burrowsianum on leaves of unidentified Poaceae, Castanediella senegaliae on dead pods of Senegalia ataxacantha, Cladophialophora behniae on leaves of Behnia sp., Colletotrichum cliviigenum on leaves of Clivia sp., Diatrype dalbergiae on bark of Dalbergia armata, Falcocladium heteropyxidicola on leaves of Heteropyxis canescens, Lapidomyces aloidendricola as epiphyte on brown stem of Aloidendron dichotomum, Lasionectria sansevieriae and Phaeosphaeriopsis sansevieriae on leaves of Sansevieria hyacinthoides, Lylea dalbergiae on Diatrype dalbergiae on bark of Dalbergia armata, Neochaetothyrina syzygii (incl. Neochaetothyrina gen. nov.) on leaves of Syzygium chordatum, Nothophaeomoniella ekebergiae (incl. Nothophaeomoniella gen. nov.) on leaves of Ekebergia pterophylla, Paracymostachys euphorbiae (incl. Paracymostachys gen. nov.) on leaf litter of Euphorbia ingens, Paramycosphaerella pterocarpi on leaves of Pterocarpus angolensis, Paramycosphaerella syzygii on leaf litter of Syzygium chordatum, Parateichospora phoenicicola (incl. Parateichospora gen. nov.) on leaves of Phoenix reclinata, Seiridium syzygii on twigs of Syzygium chordatum, Setophoma syzygii on leaves of Syzygium sp., Starmerella xylocopis from larval feed of an Afrotropical bee Xylocopa caffra, Teratosphaeria combreti on leaf litter of Combretum kraussii, Teratosphaericola leucadendri on leaves of Leucadendron sp., Toxicocladosporium pterocarpi on pods of Pterocarpus angolensis. Spain, Cortinarius bonachei with Quercus ilex in calcareus soils, Cortinarius brunneovolvatus under Quercus ilex subsp. ballota in calcareous soil, Extremopsis radicicola (incl. Extremopsis gen. nov.) from root-associated soil in a wet heathland, Russula quintanensis on acidic soils, Tubaria vulcanica on volcanic lapilii material, Tuber zambonelliae in calcareus soil. Sweden, Elaphomyces borealis on soil under Pinus sylvestris and Betula pubescens. Tanzania, Curvularia tanzanica on inflorescence of Cyperus aromaticus. Thailand, Simplicillium niveum on Ophiocordyceps camponoti-leonardi on underside of unidentified dicotyledonous leaf. USA, Calonectria californiensis on leaves of Umbellularia californica, Exophiala spartinae from surface sterilised roots of Spartina alterniflora, Neophaeococcomyces oklahomaensis from outside wall of alcohol distillery. Vietnam, Fistulinella aurantioflava on soil. Morphological and culture characteristics are supported by DNA barcodes.
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| 7. |
- Poley, L., et al.
(author)
-
The ABC130 barrel module prototyping programme for the ATLAS strip tracker
- 2020
-
In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:9
-
Journal article (peer-reviewed)abstract
- For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2, 3] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.
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| 8. |
- Crous, P. W., et al.
(author)
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Fungal Planet description sheets: 1478-1549
- 2023
-
In: Persoonia. - 0031-5850. ; 50, s. 158-310
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Australia, Aschersonia mackerrasiae on whitefly, Cladosporium corticola on bark of Melaleuca quinquenervia, Penicillium nudgee from soil under Melaleuca quinquenervia, Pseudocercospora blackwoodiae on leaf spot of Persoonia fal- cata, and Pseudocercospora dalyelliae on leaf spot of Senna alata. Bolivia, Aspicilia lutzoniana on fully submersed siliceous schist in high-mountain streams, and Niesslia parviseta on the lower part and apothecial discs of Erioderma barbellatum on a twig. Brazil, Cyathus bonsai on decaying wood, Geastrum albofibrosum from moist soil with leaf litter, Laetiporus pratigiensis on a trunk of a living unknown hardwood tree species, and Scytalidium synnematicum on dead twigs of unidentified plant. Bulgaria, Amanita abscondita on sandy soil in a plantation of Quercus suber. Canada, Penicillium acericola on dead bark of Acer saccharum, and Penicillium corticola on dead bark of Acer saccharum. China, Colletotrichum qingyuanense on fruit lesion of Capsicum annuum. Denmark, Helminthosphaeria leptospora on corticioid Neohypochnicium cremicolor. Ecuador (Galapagos), Phaeosphaeria scalesiae on Scalesia sp. Finland, Inocybe jacobssonii on calcareous soils in dry forests and park habitats. France, Cortinarius rufomyr- rheus on sandy soil under Pinus pinaster, and Periconia neominutissima on leaves of Poaceae. India, Coprinopsis fragilis on decaying bark of logs, Filoboletus keralensis on unidentified woody substrate, Penicillium sankaranii from soil, Physisporinus tamilnaduensis on the trunk of Azadirachta indica, and Poronia nagaraholensis on elephant dung. Iran, Neosetophoma fici on infected leaves of Ficus elastica. Israel, Cnidariophoma eilatica (incl. Cnidario- phoma gen. nov.) from Stylophora pistillata. Italy, Lyophyllum obscurum on acidic soil. Namibia, Aureobasidium faidherbiae on dead leaf of Faidherbia albida, and Aureobasidium welwitschiae on dead leaves of Welwitschia mirabilis. Netherlands, Gaeumannomycella caricigena on dead culms of Carex elongata, Houtenomyces caricicola (incl. Houtenomyces gen. nov.) on culms of Carex disticha, Neodacampia ulmea (incl. Neodacampia gen. nov.) on branch of Ulmus laevis, Niesslia phragmiticola on dead standing culms of Phragmites australis, Pseudopyricularia caricicola on culms of Carex disticha, and Rhodoveronaea nieuwwulvenica on dead bamboo sticks. Norway, Arrhenia similis half-buried and moss-covered pieces of rotting wood in grass-grown path. Pakistan, Mallocybe ahmadii on soil. Poland, Beskidomyces laricis (incl. Beskidomyces gen. nov.) from resin of Larix decidua ssp. polonica, Lapi- domyces epipinicola from sooty mould community on Pinus nigra, and Leptographium granulatum from a gallery of Dendroctonus micans on Picea abies. Portugal, Geoglossum azoricum on mossy areas of laurel forest areas planted with Cryptomeria japonica, and Lunasporangiospora lusitanica from a biofilm covering a biodeteriorated limestone wall. Qatar, Alternaria halotolerans from hypersaline sea water, and Alternaria qatarensis from water sample collected from hypersaline lagoon. South Africa, Alfaria thamnochorti on culm of Thamnochortus fraternus, Knufia aloeicola on Aloe gariepensis, Muriseptatomyces restionacearum (incl. Muriseptatomyces gen. nov. ) on culms of Restionaceae, Neocladosporium arctotis on nest of cases of bag worm moths (Lepidoptera, Psychidae) on Arctotis auriculata, Neodevriesia scadoxi on leaves of Scadoxus puniceus, Paraloratospora schoenoplecti on stems of Schoenoplectus lacustris, Tulasnella epidendrea from the roots of Epidendrum x obrienianum, and Xenoidriella cinnamomi (incl. Xenoidriella gen. nov.) on leaf of Cinnamomum camphora. South Korea, Lemonniera fraxinea on decaying leaves of Fraxinus sp. from pond. Spain, Atheniella lauri on the bark of fallen trees of Laurus nobilis, Halocryptovalsa endophytica from surface-sterilised, asymptomatic roots of Salicornia patula, Inocybe amygda- liolens on soil in mixed forest, Inocybe pityusarum on calcareous soil in mixed forest, Inocybe roseobulbipes on acidic soils, Neonectria borealis from roots of Vitis berlandieri x Vitis rupestris, Sympoventuria eucalyptorum on leaves of Eucalyptus sp., and Tuber conchae from soil. Sweden, Inocybe bidumensis on calcareous soil. Thailand, Cordyceps sandindaengensis on Lepidoptera pupa, buried in soil, Ophiocordyceps kuchinaraiensis on Coleoptera larva, buried in soil, and Samsoniella winandae on Lepidoptera pupa, buried in soil. Taiwan region (China), Neo- phaeosphaeria livistonae on dead leaf of Livistona rotundifolia. Turkiye, Melanogaster anatolicus on clay loamy soils. UK, Basingstokeomyces allii (incl. Basingstokeomyces gen. nov.) on leaves of Allium schoenoprasum. Ukraine, Xenosphaeropsis corni on recently dead stem of Cornus alba. USA, Nothotrichosporon aquaticum (incl. Nothotrichosporon gen. nov.) from water, and Periconia philadelphiana from swab of coil surface. Morphological and culture characteristics for these new taxa are supported by DNA barcodes.
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| 9. |
- Crous, Pedro W., et al.
(author)
-
Fungal Planet description sheets: 1383–1435
- 2022
-
In: Persoonia: Molecular Phylogeny and Evolution of Fungi. - : Naturalis Biodiversity Center. - 0031-5850 .- 1878-9080. ; 48, s. 261-371
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum laurisilvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes.
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| 10. |
- Upsdell, E. W., et al.
(author)
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The XMM cluster survey : exploring scaling relations and completeness of the dark energy survey year 3 redMaPPer cluster catalogue
- 2023
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 522:4, s. 5267-5290
-
Journal article (peer-reviewed)abstract
- We cross-match and compare characteristics of galaxy clusters identified in observations from two sky surveys using two completely different techniques. One sample is optically selected from the analysis of 3 years of Dark Energy Survey observations using the redMaPPer cluster detection algorithm. The second is X-ray selected from XMM observations analysed by the XMM Cluster Survey. The samples comprise a total area of 57.4 deg(2), bounded by the area of four contiguous XMM survey regions that overlap the DES footprint. We find that the X-ray-selected sample is fully matched with entries in the redMaPPer catalogue, above lambda > 20 and within 0.1 < z < 0.9. Conversely, only 38 per cent of the redMaPPer catalogue is matched to an X-ray extended source. Next, using 120 optically clusters and 184 X-ray-selected clusters, we investigate the form of the X-ray luminosity-temperature (L-X -T-X ), luminosity-richness (L-X - lambda), and temperature-richness (T-X - lambda) scaling relations. We find that the fitted forms of the L-X -T-X relations are consistent between the two selection methods and also with other studies in the literature. However, we find tentative evidence for a steepening of the slope of the relation for low richness systems in the X-ray-selected sample. When considering the scaling of richness with X-ray properties, we again find consistency in the relations (i.e. L-X - lambda and T-X - lambda) between the optical and X-ray-selected samples. This is contrary to previous similar works that find a significant increase in the scatter of the luminosity scaling relation for X-ray-selected samples compared to optically selected samples.
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| 11. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 12. |
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| 13. |
- Le Guen, Yann, et al.
(author)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
-
Journal article (peer-reviewed)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Mansouri, L, et al.
(author)
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Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
- 2023
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 37:2, s. 339-347
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Journal article (peer-reviewed)abstract
- Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
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| 18. |
- Leeksma, AC, et al.
(author)
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Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
- 2021
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:1, s. 87-97
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Journal article (peer-reviewed)abstract
- Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
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| 19. |
- Seyed Khoei, Nazlisadat, et al.
(author)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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