Phylogenetic classification of Cordyceps and the clavicipitaceous fungi

Cordyceps, comprising over 400 species, was historically classified in the Clavicipitaceae, based on cylindrical asci, thickened ascus apices and filiform ascospores, which often disarticulate into part-spores. Cordyceps was characterized by the production of well-developed often stipitate stromata and an ecology as a pathogen of arthropods and Elaphomyces with infrageneric classifications emphasizing arrangement of perithecia, ascospore morphology and host affiliation. To refine the classification of Cordyceps and the Clavicipitaceae, the phylogenetic relationships of 162 taxa were estimated based on analyses consisting of five to seven loci, including the nuclear ribosomal small and large subunits (nrSSU and nrLSU), the elongation factor 1α (tef1), the largest and the second largest subunits of RNA polymerase II (rpb1 and rpb2), β-tubulin (tub), and mitochondrial ATP6 (atp6). Our results strongly support the existence of three clavicipitaceous clades and reject the monophyly of both Cordyceps and Clavicipitaceae. Most diagnostic characters used in current classifications of Cordyceps (e.g., arrangement of perithecia, ascospore fragmentation, etc.) were not supported as being phylogenetically informative; the characters that were most consistent with the phylogeny were texture, pigmentation and morphology of stromata. Therefore, we revise the taxonomy of Cordyceps and the Clavicipitaceae to be consistent with the multi-gene phylogeny. The family Cordycipitaceae is validated based on the type of Cordyceps, C. militaris, and includes most Cordyceps species that possess brightly coloured, fleshy stromata. The new family Ophiocordycipitaceae is proposed based on Ophiocordyceps Petch, which we emend. The majority of species in this family produce darkly pigmented, tough to pliant stromata that often possess aperithecial apices. The new genus Elaphocordyceps is proposed for a subclade of the Ophiocordycipitaceae, which includes all species of Cordyceps that parasitize the fungal genus Elaphomyces and some closely related species that parasitize arthropods. The family Clavicipitaceae s. s. is emended and includes the core clade of grass symbionts (e.g., Balansia, Claviceps, Epichloë, etc.), and the entomopathogenic genus Hypocrella and relatives. In addition, the new genus Metacordyceps is proposed for Cordyceps species that are closely related to the grass symbionts in the Clavicipitaceae s. s. Metacordyceps includes teleomorphs linked to Metarhizium and other closely related anamorphs. Two new species are described, and lists of accepted names for species in Cordyceps, Elaphocordyceps, Metacordyceps and Ophiocordyceps are provided

Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection

<p>Abstract</p> <p>Background</p> <p>Parasites that manipulate host behavior can provide prominent examples of extended phenotypes: parasite genomes controlling host behavior. Here we focus on one of the most dramatic examples of behavioral manipulation, the death grip of ants infected by <it>Ophiocordyceps </it>fungi. We studied the interaction between <it>O. unilateralis s.l</it>. and its host ant <it>Camponotus leonardi </it>in a Thai rainforest, where infected ants descend from their canopy nests down to understory vegetation to bite into abaxial leaf veins before dying. Host mortality is concentrated in patches (graveyards) where ants die on sapling leaves <it>ca</it>. 25 cm above the soil surface where conditions for parasite development are optimal. Here we address whether the sequence of ant behaviors leading to the final death grip can also be interpreted as parasite adaptations and describe some of the morphological changes inside the heads of infected workers that mediate the expression of the death grip phenotype.</p> <p>Results</p> <p>We found that infected ants behave as zombies and display predictable stereotypical behaviors of random rather than directional walking, and of repeated convulsions that make them fall down and thus precludes returning to the canopy. Transitions from erratic wandering to death grips on a leaf vein were abrupt and synchronized around solar noon. We show that the mandibles of ants penetrate deeply into vein tissue and that this is accompanied by extensive atrophy of the mandibular muscles. This lock-jaw means the ant will remain attached to the leaf after death. We further present histological data to show that a high density of single celled stages of the parasite within the head capsule of dying ants are likely to be responsible for this muscular atrophy.</p> <p>Conclusions</p> <p>Extended phenotypes in ants induced by fungal infections are a complex example of behavioral manipulation requiring coordinated changes of host behavior and morphology. Future work should address the genetic basis of such extended phenotypes.</p

New 1F1N Species Combinations in Ophiocordycipitaceae (Hypocreales)

Abstract Based on the taxonomic and nomenclatural recommendations of Quandt et al. (2014) new species combinations are made for Ophiocordycipitaceae. These new combinations are compliant with recent changes in the International Code of Nomenclature for algae, fungi, and plants (ICN) and the abolition of the dual system of nomenclature for fungi. These changes include 10 new combinations into Drechmeria, four new combinations into Harposporium, 23 new combinations and 15 synonymies in Ophiocordyceps, and one new combination into Purpureocillium.https://deepblue.lib.umich.edu/bitstream/2027.42/149189/1/43008_2015_Article_602357.pd

Graveyards on the Move: The Spatio-Temporal Distribution of Dead Ophiocordyceps-Infected Ants

Parasites are likely to play an important role in structuring host populations. Many adaptively manipulate host behaviour, so that the extended phenotypes of these parasites and their distributions in space and time are potentially important ecological variables. The fungus Ophiocordyceps unilateralis, which is pan-tropical in distribution, causes infected worker ants to leave their nest and die under leaves in the understory of tropical rainforests. Working in a forest dynamic plot in Southern Thailand we mapped the occurrence of these dead ants by examining every leaf in 1,360 m2 of primary rainforest. We established that high density aggregations exist (up to 26 dead ants/m2), which we coined graveyards. We further established that graveyards are patchily distributed in a landscape with no or very few O. unilateralis-killed ants. At some, but not all, spatial scales of analysis the density of dead ants correlated with temperature, humidity and vegetation cover. Remarkably, having found 2243 dead ants inside graveyards we only found 2 live ants of the principal host, ant Camponotus leonardi, suggesting that foraging host ants actively avoid graveyards. We discovered that the principal host ant builds nests in high canopy and its trails only occasionally descend to the forest floor where infection occurs. We advance the hypothesis that rare descents may be a function of limited canopy access to tree crowns and that resource profitability of such trees is potentially traded off against the risk of losing workers due to infection when forest floor trails are the only access routes. Our work underscores the need for an integrative approach that recognises multiple facets of parasitism, such as their extended phenotypes

Emollient bath additives for the treatment of childhood eczema (BATHE): multi-centre pragmatic parallel group randomised controlled trial of clinical and cost-effectiveness

Objectives: To determine the clinical and cost-effectiveness of including emollient bath additives in the management of childhood eczema. Trial design: Pragmatic randomised open-label superiority trial with two parallel groups. Setting and recruitment: 96 general practices in Wales, West of England and Southern England. Invitation by personal letter or opportunistically by usual clinical team. Participants: Children were eligible to participate if aged over 12 months and less than 12 years, fulfilling UK Diagnostic Criteria for Atopic Dermatitis. Children with inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once a week, or whose carers were not willing to accept randomisation. 483 were randomised and one withdrew, leaving 482 children in the trial: 51% female, 84% white, mean age 5 years. Interventions: The intervention group were prescribed emollient bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management and were given standardised advice on how to wash. Primary outcome: Eczema control measured by Patient Oriented Eczema Measure (POEM, range 0-28) weekly for 16 weeks. Secondary outcomes: Eczema severity over 1 year (4-weekly POEM from baseline to 52 weeks); number of eczema exacerbations resulting in primary healthcare consultation; disease-specific quality of life (QOL) (Dermatitis Family Impact); generic QoL (Child Health Utility-9D); resource utilisation; type and quantity of topical corticosteroid/calcineurin inhibitors prescribed. Randomisation: 483 children were randomised (1:1) using online software, stratified by recruiting centre. Results: 95.6% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 76.8% (370/482) of participants completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean Baseline POEM was 9.5 (s.d. 5.7) in the bath additives group and 10.1 (s.d. 5.8) in the no bath additives group. The mean POEM over the 16-week period was 7.5 (s.d. 6.0) in the bath additives group and 8.4 (6.0) in the no bath additives group. There was no statistically significant difference in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% CI -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. There was no difference between groups in secondary outcomes, economic outcomes or in adverse effects. Conclusions: This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of childhood eczema. Further research is needed into optimal regimens for leave-on emollient and use of soap substitutes for children with eczema

The Life of a Dead Ant:The Expression of an Adaptive Extended Phenotype

Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings similar to 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth. Experimental relocation confirmed that parasite fitness was lower outside this manipulative zone. Host resources were rapidly colonized and further secured by extensive internal structuring. Nutritional composition analysis indicated that such structuring allows the parasite to produce a large fruiting body for spore production. Our findings suggest that the osmotrophic lifestyle of fungi may have facilitated novel exploitation strategies

Nation, state and identity in international sport

The question of eligibility for international sporting representation (ISR) has become increasingly contentious. In this paper we argue that the current ISR regulations are outdated and problematic. Sporting governing bodies ought to ignore citizenship as a criterion for ISR, and instead ISR should be based on a normative account of national belonging which would operate primarily on grounds of early socialisation and longterm residency. This approach would avoid many of the pragmatic and moral pathologies of ISR, and would utilise sports potential in promoting a liberal and progressive understanding of national ties

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP. KEYWORDS: Craniopharyngioma; IL1-β; Inflammasome; MAPK/ERK pathway; Odontogenesis; Paracrine signalling; Trametini