A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

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 Smilaxglyciphylla. 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. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.

Evaluating methodologies for species delimitation: the mismatch between phenotypes and genotypes in lichenized fungi (Bryoria sect. Implexae, Parmeliaceae).

In many lichen-forming fungi, molecular phylogenetic analyses lead to the discovery of cryptic species within traditional morphospecies. However, in some cases, molecular sequence data also questions the separation of phenotypically characterised species. Here we apply an integrative taxonomy approach - including morphological, chemical, molecular, and distributional characters - to re-assess species boundaries in a traditionally speciose group of hair lichens, Bryoria sect. Implexae. We sampled multilocus sequence and microsatellite data from 142 specimens from a broad intercontinental distribution. Molecular data included DNA sequences of the standard fungal markers ITS, IGS, GAPDH, two newly tested loci (FRBi15 and FRBi16), and SSR frequencies from 18 microsatellite markers. Datasets were analysed with Bayesian and maximum likelihood phylogenetic reconstruction, phenogram reconstruction, STRUCTURE Bayesian clustering, principal coordinate analysis, haplotype network, and several different species delimitation analyses (ABGD, PTP, GMYC, and DISSECT). Additionally, past population demography and divergence times are estimated. The different approaches to species recognition do not support the monophyly of the 11 currently accepted morphospecies, and rather suggest the reduction of these to four phylogenetic species. Moreover, three of these are relatively recent in origin and cryptic, including phenotypically and chemically variable specimens. Issues regarding the integration of an evolutionary perspective into taxonomic conclusions in species complexes, which have undergone recent diversification, are discussed. The four accepted species, all epitypified by sequenced material, are Bryoria fuscescens, B. glabra, B. kockiana, and B. pseudofuscescens. Ten species rank names are reduced to synonymy. In the absence of molecular data, they can be recorded as the B. fuscescens complex. Intraspecific phenotype plasticity and factors affecting the speciation of different morphospecies in this group of Bryoria are outlined.

Endophytic and endolichenic fungal diversity in maritime Antarctica based on cultured material and their evolutionary position among Dikarya.

Fungal endophytes comprise one of the most ubiquitous groups of plant symbionts. They live asymptomatically within vascular plants, bryophytes and also in close association with algal photobionts inside lichen thalli. While endophytic diversity in land plants has been well studied, their diversity in lichens and bryophytes are poorly understood. Here, we compare the endolichenic and endophytic fungal communities isolated from lichens and bryophytes in the Barton Peninsula, King George Island, Antarctica. A total of 93 fungal isolates were collected from lichens and bryophytes. In order to determine their identities and evolutionary relationships, DNA sequences of the nuclear internal transcribed spacer (ITS), nuclear ribosomal small subunit (nuSSU), nuclear large subunit (nuLSU), and mitochondrial SSU (mtSSU) rDNA were obtained and protein coding markers of the two largest subunit of RNA polymerase II (RPB1 and RPB2) were generated. Multilocus phylogenetic analyses revealed that most of the fungal isolates were distributed in the following six classes in the phylum Ascomycota: Dothideomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Pezizomycetes and Sordariomycetes. For the first time we report the presence of subphylum Mortierellomycotina that may belong to an undescribed order in endophytic fungi. Taken together, our results imply that lichens and bryophytes provide similar niches and harbour a selection of these fungi, indicating generalists within the framework of evolutionary adaptation.

Evaluation of the Antioxidant Capacities and Cytotoxic Effects of Ten Parmeliaceae Lichen Species.

Parmeliaceae represents the largest and widespread family of lichens and includes species that attract much interest regarding pharmacological activities, due to their production of unique secondary metabolites. The current work aimed to investigate the in vitro antioxidant and cytotoxic activities of the methanol extracts of ten Parmeliaceae species, collected in different continents. Methanol extraction afforded high phenolic content in the extracts. The antioxidant activity displayed by lichens was evaluated through chemical assays, such as the ORAC (Oxygen Radical Absorbance Capacity) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and the ferric reducing antioxidant power (FRAP). A moderately positive correlation was found between the phenolic content and the antioxidant properties for all the species: R: 0.7430 versus ORAC values, R: 0.7457 versus DPPH scavenging capacity, and R: 0.7056 versus FRAP reducing power. The methanol extract of Flavoparmelia euplecta exhibited the highest ORAC value, the extract of Myelochroa irrugans showed the maximum DPPH scavenging capacity, and Hypotrachyna cirrhata methanol extract demonstrated the highest reducing power. Further, the cytotoxic activity of the ten species was investigated on the human cancer cell lines HepG2 and MCF-7; Myelochroa irrugans exhibited the highest anticancer potential. The pharmacological activities shown here could be attributed to their phytochemical constituents.

New primers for promising single-copy genes in fungal phylogenetics and systematics.

Developing powerful phylogenetic markers is a key concern in fungal phylogenetics. Here we report degenerate primers that amplify the single-copy genes Mcm7 (MS456) and Tsr1 (MS277) across a wide range of Pezizomycotina (Ascomycota). Phylogenetic analyses of 59 taxa belonging to the Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes and Sordariomycetes, indicate the utility of these loci for fungal phylogenetics at taxonomic levels ranging from genus to class. We also tested the new primers in silico using sequences of Saccharomycotina, Taphrinomycotina and Basidiomycota to predict their potential of amplifying widely across the Fungi. The analyses suggest that the new primers will need no, or only minor sequence modifications to amplify Saccharomycotina, Taphrinomycotina and Basidiomycota.