Aphyllophoroid funga (Basidiomycota) of Finland : range extensions and records of nationally new and rare species

Knowledge of the Finnish aphyllophoroid funga has increased substantially in recent years. In this article, we present two species new to Finland: Spiculogloea subminuta Hauerslev and Typhula suecica I. Olariaga, G. Corriol, I. Salcedo & K. Hansen, and document Sistotrema luteoviride Kotir. & K.-H. Larss. for the third time globally. We also contribute 50 new records of 33 nationally rare species (with a maximum of ten previous records in Finland) and list 52 regionally new species, found for the first time in a certain subzone of the boreal vegetation zone in Finland. Each record is enclosed and contains notes on the substrate. Furthermore, the ecology of the nationally new species and the distribution of rare species are discussed

Probing of Exosites Leads to Novel Inhibitor Scaffolds of HCV NS3/4A Proteinase

Hepatitis C is a treatment-resistant disease affecting millions of people worldwide. The hepatitis C virus (HCV) genome is a single-stranded RNA molecule. After infection of the host cell, viral RNA is translated into a polyprotein that is cleaved by host and viral proteinases into functional, structural and non-structural, viral proteins. Cleavage of the polyprotein involves the viral NS3/4A proteinase, a proven drug target. HCV mutates as it replicates and, as a result, multiple emerging quasispecies become rapidly resistant to anti-virals, including NS3/4A inhibitors.To circumvent drug resistance and complement the existing anti-virals, NS3/4A inhibitors, which are additional and distinct from the FDA-approved telaprevir and boceprevir α-ketoamide inhibitors, are required. To test potential new avenues for inhibitor development, we have probed several distinct exosites of NS3/4A which are either outside of or partially overlapping with the active site groove of the proteinase. For this purpose, we employed virtual ligand screening using the 275,000 compound library of the Developmental Therapeutics Program (NCI/NIH) and the X-ray crystal structure of NS3/4A as a ligand source and a target, respectively. As a result, we identified several novel, previously uncharacterized, nanomolar range inhibitory scaffolds, which suppressed of the NS3/4A activity in vitro and replication of a sub-genomic HCV RNA replicon with a luciferase reporter in human hepatocarcinoma cells. The binding sites of these novel inhibitors do not significantly overlap with those of α-ketoamides. As a result, the most common resistant mutations, including V36M, R155K, A156T, D168A and V170A, did not considerably diminish the inhibitory potency of certain novel inhibitor scaffolds we identified.Overall, the further optimization of both the in silico strategy and software platform we developed and lead compounds we identified may lead to advances in novel anti-virals

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Uphill Shifts of Fungal Fruiting Due to Climate Change at the Polar Urals

Due to the ongoing climatic changes in the Arctic, the ranges of many plants and animal species are rising higher into the mountains, into the treeline; however, such studies are rare for fungi. The 60-year fruiting dynamics of 66 species of Agaricomycetous macrofungi has been studied along the altitudinal transect located on the slope of Slantsevaya Mountain (Polar Urals, Russia). It has been found that the three basic trophic groups (mycorrhizal, saprobes on litter and soil, and saprobes on wood) fruit higher in the mountains. Additionally, for most of the studied species, a tendency towards upward displacement of fruiting was revealed. The rise in fruiting for saprobes on litter and soil was the most obvious. Mycorrhizal fungi associated with woody plants showed the least uplifting effect. Fungal species that were characterized by fruiting higher up the mountainside half a century ago show stronger upward shifts compared to species previously bearing fruit only at the mountain foot. Probably, such a reaction of the aboveground mycobiota is similar to the processes occurring in the soil, which are associated with an active increase in the decomposition rate of the litter, an increase in the depth of permafrost thawing, and a significant redistribution of the soil water balance. On the other hand, the rise of fungi is associated with an increase of plant biomass in the middle and upper parts, which are the most important sources of fungal nutrition

Relationship between Species Richness, Biomass and Structure of Vegetation and Mycobiota along an Altitudinal Transect in the Polar Urals

Aboveground species richness patterns of vascular plants, aphyllophoroid macrofungi, bryophytes and lichens were compared along an altitudinal gradient (80–310 m a.s.l.) on the Slantsevaya mountain at the eastern macroslope of the Polar Urals (Russia). Five altitudinal levels were included in the study: (1) Northern boreal forest with larch-spruce in the Sob’ river valley habitats; (2–3) two levels of closed, northern boreal, larch-dominated forests on the slopes; (4) crook-stemmed forest; (5) tundra habitats above the timberline. Vascular plant or bryophyte species richness was not affected by altitudinal levels, but lichen species richness significantly increased from the river valley to the tundra. For aphyllophoroid macrofungi, species richness was highest at intermediate and low altitudes, and poorest in the tundra. These results indicate a positive ecotone effect on aphyllophoroid fungal species richness. The species richness of aphyllophoroid fungi as a whole was neither correlated to mortmass stocks, nor to species richness of vascular plants, but individual ecological or morphological groups depended on these parameters. Poroid fungal species richness was positively correlated to tree age, wood biomass and crown density, and therefore peaked in the middle of the slope and at the foot of the mountain. In contrast, clavarioid fungal species richness was negatively related to woody bio- and mortmass, and therefore peaked in the tundra. This altitudinal level was characterized by high biomass proportions of lichens and mosses, and by high litter mortmass. The proportion of corticoid fungi increased with altitude, reaching its maximum at the timberline. Results from the different methods used in this work were concordant, and showed significant patterns. Tundra communities differ significantly from the forest communities, as is also confirmed by nonmetric multidimensional scaling (NMDS) analyses based on the spectrum of morphological and ecological groups of aphyllophoroid fungi

Longitudinal changes of clavarioid funga (Basidiomycota) diversity in the tundra zone of Eurasia

The study deals with certain variations of the diversity level of clavarioid funga in the 33 localities (100 km2 each) inside seven longitudinal sectors (100,000 km2) situated along the gradient of the climatic continentality of the Eurasian tundra zone. As continentality increases, from the maritime climate of Fennoscandia to the continental climate of Yakutia, α-diversity and γ-diversity decrease considerably. On the other side, spatial turnover of species, or β-diversity, grows in the direction of continental areas. This paper uses the following methods to assess the spatial turnover: Whittaker’s index and mean Jaccard similarity index, as well as by several other parameters. In addition, our data show that the genus Typhula is richest in the tundra, and its share in the structure of the clavarioid funga grows as the studied area decreases, as well as when the environmental conditions become more severe (continentality of the climate). Also, the paper discusses the issue of newly emerging taiga fungi species in the European Arctic, which is connected with climatic warming followed by ″greening″ of the tundra. Note that in the cryo-semiarid continental climate of Yakutia, where climatic changes are just as pronounced, no new taxons have been discovered so far