Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

$\textbf{BACKGROUND}$: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. $\textbf{METHODS AND FINDINGS}$: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. $\textbf{CONCLUSIONS}$: Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.MRC Epidemiology Unit, Fenland study, EPIC-InterAct study, EPIC-Norfolk case-cohort study funding: this study was funded by the United Kingdom’s Medical Research Council through grants MC_UU_12015/1, MC_UU_12015/5, MC_PC_13046, MC_PC_13048 and MR/L00002/1. We acknowledge support from the National Institute for Health Research Biomedical Research Centre. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. EPIC-InterAct Study funding: funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). MRC Human Nutrition Research funding: This research was supported by the Medical Research Council (MC_UP_A090_1006) and Cambridge Lipidomics Biomarker Research Initiative (G0800783). The SABRE study was funded at baseline by the UK Medical Research Council, Diabetes UK and the British Heart Foundation and at follow-up by a programme grant from the Wellcome Trust (WT082464) and British Heart Foundation (SP/07/001/23603); Diabetes UK funded the metabolomics analyses (13/0004774). RJOS, EN, JRZ and AK received funding from the Swedish Research Council, Stockholm County Council, Novo Nordisk Foundation and Diabetes Wellness. DBS is supported by the Wellcome Trust grant number 107064. MIM is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. IB is supported by the Wellcome Trust grant WT098051

Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: a mendelian randomisation analysis

BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. CONCLUSIONS: Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes

Development and characterisation of novel electrospun polylactic acid/tubular clay nanocomposites

A novel material formulation method of polylactic acid /tubular clay nanocomposites via electrospinning was introduced and the important processing parameters such as solution concentration, clay loading, material feed rate were particularly investigated. The hybrid fibre diameter, the clay dispersability and the thermal properties of such nanocomposites were then characterised by using the scanning electron microscopy, wide-angle X-ray diffraction and differential scanning calorimetry, respectively, to establish a fundamental structure–property relationship for the future application

Desafíos políticos de los países de inmigración

13 págs.-- Publicado en "Confluencia XXI. Revista de Pensamiento Político" (México), nº 3 (Oct-Dic 2008) bajo el título monográfico "Migrantes: ¿Por qué se van? ¿Por qué se quedan?".Las migraciones, una práctica tan antigua como la propia condición humana, se han convertido en un factor estructural de primer orden, en uno de los macrofenómenos más definitorios de nuestra época y en un complejo reto para las sociedades contemporáneas. En prácticamente todos los países del mundo, todo lo que concierne a este complejo fenómeno ocupa un lugar destacado en la agenda política. La gestión, el control y la integración de los movimientos internacionales de personas se presentan como un policy field de creciente y prioritaria relevancia. No se trata, sin embargo, de una cuestión de mera moda: el número de países implicados de manera significativa en las migraciones internacionales ha aumentado considerablemente, hasta el punto de que resulta realmente difícil encontrar algún Estado que no sea bien un país de inmigración, bien un país de emigración o bien ambas cosas a la vez, cuando no al menos un país de tránsito. No ha de extrañar entonces que la mayoría de los gobiernos haya tomado conciencia de la necesidad de ofrecer una respuesta en términos legales e institucionales a un fenómeno de carácter permanente que puede llegar a alterar la estructura demográfica, social, cultural, económica y laboral de un país. Dada la complejidad de la cuestión, y por cuestiones de economía argumentativa, aquí se abordará de manera fundamental desde la perspectiva de los países receptores, que, por lo demás, es también la adoptada en forma habitual por los países europeos que registran mayor inmigración. Sin embargo, el fenómeno migratorio es fundamentalmente transnacional y tiene fehacientes repercusiones en los países de emigración.Peer reviewe

Fungal Planet description sheets: 1436–1477

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilax glyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes

An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

Fungal Planet description sheets: 1182–1283

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 а 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

Fungal Planet description sheets: 1182-1283

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 indoor oopillyensis, 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. [...]Leslie W.S. de Freitas and colleagues express their gratitude to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarships provided to Leslie Freitas and for the research grant provided to André Luiz Santiago; their contribution was financed by the projects ‘Diversity of Mucoromycotina in the different ecosystems of the Atlantic Rainforest of Pernambuco’ (FACEPE–First Projects Program PPP/ FACEPE/CNPq–APQ–0842-2.12/14) and ‘Biology of conservation of fungi s.l. in areas of Atlantic Forest of Northeast Brazil’ (CNPq/ICMBio 421241/ 2017-9) H.B. Lee was supported by the Graduate Program for the Undiscovered Taxa of Korea (NIBR202130202). The study of O.V. Morozova, E.F. Malysheva, V.F. Malysheva, I.V. Zmitrovich, and L.B. Kalinina was carried out within the framework of a research project of the Komarov Botanical Institute RAS (АААА-А19-119020890079-6) using equipment of its Core Facility Centre ‘Cell and Molecular Technologies in Plant Science’. The work of O. V. Morozova, L.B. Kalinina, T. Yu. Svetasheva, and E.A. Zvyagina was financially supported by Russian Foundation for Basic Research project no. 20-04-00349. E.A. Zvyagina and T.Yu. Svetasheva are grateful to A.V. Alexandrova, A.E. Kovalenko, A.S. Baykalova for the loan of specimens, T.Y. James, E.F. Malysheva and V.F. Malysheva for sequencing. J.D. Reyes acknowledges B. Dima for comparing the holotype sequence of Cortinarius bonachei with the sequences in his database. A. Mateos and J.D. Reyes acknowledge L. Quijada for reviewing the phylogeny and S. de la Peña- Lastra and P. Alvarado for their support and help. Vladimir I. Kapitonov and colleagues are grateful to Brigitta Kiss for help with their molecular studies. This study was conducted under research projects of the Tobolsk Complex Scientific Station of the Ural Branch of the Russian Academy of Sciences (N АААА-А19-119011190112-5). E. Larsson acknowledges the Swedish Taxonomy Initiative, SLU Artdatabanken, Uppsala (dha.2019.4.3-13). The study of D.B. Raudabaugh and colleagues was supported by the Schmidt Science Fellows, in partnership with the Rhodes Trust. Gregorio Delgado is grateful to Michael Manning and Kamash Pillai (Eurofins EMLab P&K) for provision of laboratory facilities. Jose G. Maciá-Vicente acknowledges support from the German Research Foundation under grant MA7171/1-1, and from the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the state of Hesse within the framework of the Cluster for Integrative Fungal Research (IPF). Thanks are also due to the authorities of the Cabañeros National Park and Los Alcornocales Natural Park for granting the collection permit and for support during field work. The study of Alina V. Alexandrova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121032300081-7. Michał Gorczak was financially supported by the Ministry of Science and Higher Education through the Faculty of Biology, University of Warsaw intramural grant DSM 0117600- 13. M. Gorczak acknowledges M. Klemens for sharing a photo of the Białowieża Forest logging site and M. Senderowicz for help with preparing the illustration. Ivona Kautmanová and D. Szabóová were funded by the Operational Program of Research and Development and co-financed with the European Fund for Regional Development (EFRD). ITMS 26230120004: ‘Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative’. Ishika Bera, Aniket Ghosh, Jorinde Nuytinck and Annemieke Verbeken are grateful to the Director, Botanical Survey of India (Kolkata), Head of the Department of Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar, Garhwal for providing research facilities. Ishika Bera and Aniket Ghosh acknowledge the staff of the forest department of Arunachal Pradesh for facilitating the macrofungal surveys to the restricted areas. Sergey Volobuev was supported by the Russian Science Foundation (RSF project N 19-77- 00085). Aleksey V. Kachalkin and colleagues were supported by the Russian Science Foundation (grant No. 19-74-10002). The study of Anna M. Glushakova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121040800174-6. Tracey V. Steinrucken and colleagues were supported by AgriFutures Australia (Rural Industries Research and Development Corporation), through funding from the Australian Government Department of Agriculture, Water and the Environment, as part of its Rural Research and Development for Profit program (PRJ-010527). Neven Matočec and colleagues thank the Croatian Science Foundation for their financial support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). Ana Pošta thanks the Croatian Science Foundation for their support under the grant HRZZ-2018-09-7081. The research of Milan Spetik and co-authors was supported by Internal Grant of Mendel University in Brno No. IGAZF/ 2021-SI1003. K.C. Rajeshkumar thanks SERB, the Department of Science and Technology, Government of India for providing financial support under the project CRG/2020/000668 and the Director, Agharkar Research Institute for providing research facilities. Nikhil Ashtekar thanks CSIR-HRDG, INDIA, for financial support under the SRF fellowship (09/670(0090)/2020-EMRI), and acknowledges the support of the DIC Microscopy Facility, established by Dr Karthick Balasubramanian, B&P (Plants) Group, ARI, Pune. The research of Alla Eddine Mahamedi and co-authors was supported by project No. CZ.02.1.01/0.0/0.0/16_017/0002334, Czech Republic. Tereza Tejklová is thanked for providing useful literature. A. Polhorský and colleagues were supported by the Operational Program of Research and Development and co-financed with the European fund for Regional Development (EFRD), ITMS 26230120004: Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative. Yu Pei Tan and colleagues thank R. Chen for her technical support. Ernest Lacey thanks the Cooperative Research Centres Projects scheme (CRCPFIVE000119) for its support. Suchada Mongkolsamrit and colleagues were financially supported by the Platform Technology Management Section, National Center for Genetic Engineering and Biotechnology (BIOTEC), Project Grant No. P19-50231. Dilnora Gouliamova and colleagues were supported by a grant from the Bulgarian Science Fund (KP-06-H31/19). The research of Timofey A. Pankratov was supported by the Russian Foundation for Basic Research (grant No. 19-04-00297a). Gabriel Moreno and colleagues wish to express their gratitude to L. Monje and A. Pueblas of the Department of Drawing and Scientific Photography at the University of Alcalá for their help in the digital preparation of the photographs, and to J. Rejos, curator of the AH herbarium, for his assistance with the specimens examined in the present study. Vit Hubka was supported by the Charles University Research Centre program No. 204069. Alena Kubátová was supported by The National Programme on Conservation and Utilization of Microbial Genetic Resources Important for Agriculture (Ministry of Agriculture of the Czech Republic). The Kits van Waveren Foundation (Rijksherbariumfonds Dr E. Kits van Waveren, Leiden, Netherlands) contributed substantially to the costs of sequencing and travelling expenses for M. Noordeloos. The work of B. Dima was supported by the ÚNKP-20-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, and by the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office of Hungary (TKP2020-IKA-05). The Norwegian Entoloma studies received funding from the Norwegian Biodiversity Information Centre (NBIC), and the material was partly sequenced through NorBOL. Gunnhild Marthinsen and Katriina Bendiksen (Natural History Museum, University of Oslo, Norway) are acknowledged for performing the main parts of the Entoloma barcoding work. Asunción Morte is grateful to AEI/FEDER, UE (CGL2016-78946-R) and Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia (20866/PI/18) for financial support. Vladimír Ostrý was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (National Institute of Public Health – NIPH, IN 75010330). Konstanze Bensch (Westerdijk Fungal Biodiversity Institute, Utrecht) is thanked for correcting the spelling of various Latin epithets.Peer reviewe