Trichoderma songyi sp. nov., a new species associated with the pine mushroom (Tricholoma matsutake).

A new species, Trichoderma songyi, was found to be associated with the pine mushroom (Tricholoma matsutake) in Korea. This species was isolated from three different substrates: Tricholoma matsutake basidiomata, as well as roots of Pinus densiflora and soil in the fairy ring. Based on its molecular and phenotypic characteristics, we demonstrate that Trichoderma songyi is unique and distinguishable from closely related species. We performed phylogenetic analyses based on two molecular markers, the genes for both translation elongation factor 1-alpha and the second largest subunit of RNA polymerase II. Phylogenetic analyses showed that Trichoderma songyi is closely related to Trichoderma koningii aggregate and Trichoderma caerulescens. Morphologically, Trichoderma songyi can be distinguished from these closely related taxa by its growth rates, colony morphology on PDA in darkness, and coconut-like odour. Due to the economic importance of the pine mushroom, the relationship between Trichoderma songyi and Tricholoma matsutake should be studied further.

Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.

BACKGROUND: Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. METHODS: We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. RESULTS: We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. CONCLUSIONS: We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.

Pharmacist-Led Discharge Transitions of Care Interventions for Pediatric Patients: A Narrative Review.

Transitions of care (TOC) before, during, and after hospital discharge are an opportune setting to optimize medication management. The quality standards for pediatric care transitions, however, are lacking, leading to reduced health outcomes in children. This narrative review characterizes the pediatric populations that would benefit from focused, TOC interventions. Different types of medication-focused TOC interventions during hospital discharge are described, including medication reconciliation, education, access, and adherence tools. Various TOC intervention delivery models following hospital discharge are also reviewed. The goal of this narrative review is to help pediatric pharmacists and pharmacy leaders better understand TOC interventions and integrate them into the hospital discharge process for children and their caregivers.

Potential for transmission of naturally mutated H10N1 avian influenza virus to mammalian hosts and causing severe pulmonary disease.

Subtype H10 avian influenza viruses (AIV) are distributed worldwide in wild aquatic birds, and can infect humans and several other mammalian species. In the present study, we investigated the naturally mutated PB2 gene in A/aquatic bird/South Korea/SW1/2018 (A/SW1/18, H10N1), isolated from wild birds during the 2018-2019 winter season. This virus was originally found in South Korea, and is similar to isolates from mainland China and Mongolia. It had low pathogenicity, lacked a multi-basic cleavage site, and showed a binding preference for α2,3-linked sialic acids. However, it can infect mice, causing severe disease and lung pathology. SW1 was also transmitted by direct contact in ferrets, and replicated in the respiratory tract tissue, with no evidence of extrapulmonary spread. The pathogenicity and transmissibility of SW1 in mouse and ferret models were similar to those of the pandemic strain A/California/04/2009 (A/CA/04, H1N1). These factors suggest that subtype H10 AIVs have zoonotic potential and may transmit from human to human, thereby posing a potential threat to public health. Therefore, the study highlights the urgent need for closer monitoring of subtype H10 AIVs through continued surveillance of wild aquatic birds.

The shaping of cancer genomes with the regional impact of mutation processes.

Mutation signature analysis has been used to infer the contributions of various DNA mutagenic-repair events in individual cancer genomes. Here, we build a statistical framework using a multinomial distribution to assign individual mutations to their cognate mutation signatures. We applied it to 47 million somatic mutations in 1925 publicly available cancer genomes to obtain a mutation signature map at the resolution of individual somatic mutations. Based on mutation signature-level genetic-epigenetic correlative analyses, mutations with transcriptional and replicative strand asymmetries show different enrichment patterns across genomes, and "transcribed" chromatin states and gene boundaries are particularly vulnerable to transcription-coupled repair activities. While causative processes of cancer-driving mutations can be diverse, as shown for converging effects of multiple mutational processes on TP53 mutations, the substantial fraction of recurrently mutated amino acids points to specific mutational processes, e.g., age-related C-to-T transition for KRAS p.G12 mutations. Our investigation of evolutionary trajectories with respect to mutation signatures further revealed that candidate pairs of early- vs. late-operative mutation processes in cancer genomes represent evolutionary dynamics of multiple mutational processes in the shaping of cancer genomes. We also observed that the local mutation clusters of kataegis often include mutations arising from multiple mutational processes, suggestive of a locally synchronous impact of multiple mutational processes on cancer genomes. Taken together, our examination of the genome-wide landscape of mutation signatures at the resolution of individual somatic mutations shows the spatially and temporally distinct mutagenesis-repair-replication histories of various mutational processes and their effects on shaping cancer genomes.

Transcriptional Profiling Reveals Mesenchymal Subtypes of Small Cell Lung Cancer with Activation of the Epithelial-to-Mesenchymal Transition and Worse Clinical Outcomes.

While molecular subtypes of small cell lung cancers (SCLC) based on neuroendocrine (NE) and non-NE transcriptional regulators have been established, the association between these molecular subtypes and recently recognized SCLC-inflamed (SCLC-I) tumors is less understood. In this study, we used gene expression profiles of SCLC primary tumors and cell lines to discover and characterize SCLC-M (mesenchymal) tumors distinct from SCLC-I tumors for molecular features, clinical outcomes, and cross-species developmental trajectories. SCLC-M tumors show elevated epithelial-to-mesenchymal transformation (EMT) and YAP1 activity but a low level of anticancer immune activity and worse clinical outcomes than SCLC-I tumors. The prevalence of SCLC-M tumors was 3.2-7.4% in primary SCLC cohorts, which was further confirmed by immunohistochemistry in an independent cohort. Deconvoluted gene expression of tumor epithelial cells showed that EMT and increased immune function are tumor-intrinsic characteristics of SCLC-M and SCLC-I subtypes, respectively. Cross-species analysis revealed that human primary SCLC tumors recapitulate the NE-to-non-NE progression murine model providing insight into the developmental relationships among SCLC subtypes, e.g., early NE (SCLC-A and -N)- vs. late non-NE tumors (SCLC-M and -P). Newly identified SCLC-M tumors are biologically and clinically distinct from SCLC-I tumors which should be taken into account for the diagnosis and treatment of the disease.

Teach BIG: A framework-based approach to online teaching and learning.

INTRODUCTION: Cultivating a rich, engaging learning atmosphere in the online environment can be challenging for even the most seasoned educators. Technologies are rapidly advancing, traditional classroom teaching strategies are integrating into the online arena, and students and faculty are evolving to meet the demands of their new learning environments. PERSPECTIVE: One method to enhance teaching and learning in the online environment is the framework-based approach, summarized here as teach "BIG." Teach "BIG" stands for a three-pronged method that incorporates creating balance, increasing engagement, and giving resources for success. IMPLICATIONS: Incorporation of the techniques described here can enhance online teaching in the didactic, hybrid, and experiential settings. While these are not all-inclusive means, the teach "BIG" approach may provide a foundation upon which to build successful online educational programs.

Human kidney organoids reveal the role of glutathione in Fabry disease.

Fabry disease is an X-linked lysosomal storage disease caused by a mutation in the galactosidase alpha (GLA) gene. Despite advances in therapeutic technologies, the lack of humanized experimental models of Fabry disease has limited the development of new therapies to cure the disease. Herein, we modeled Fabry disease using human inducible pluripotent stem cell (iPSC)-derived kidney organoids and the CRISPR-Cas9 genome-editing system. GLA-mutant human kidney organoids revealed deformed podocytes and tubular cells with accumulation of globotriaosylceramide (Gb3). Ultrastructural analysis showed abundant electron-dense granular deposits and electron-dense lamellate lipid-like deposits that formed concentric bodies (zebra bodies) in the cytoplasm of podocytes and tubules. The oxidative stress level was increased in GLA-mutant kidney organoids, and the increase was accompanied by apoptosis. Enzyme replacement treatment (ERT) with recombinant human α-Gal A decreased the Gb3 accumulation and oxidative stress, which resulted in amelioration of the deformed cellular structure of the GLA-mutant kidney organoids. Transcription profile analyses showed decreased glutathione (GSH) metabolism in GLA-mutant kidney organoids. GSH replacement treatment decreased oxidative stress and attenuated the structural deformity of the GLA-mutant kidney organoids. GSH treatment also increased the expression of podocyte and tubular markers and decreased apoptosis. In conclusion, GLA-mutant kidney organoids derived from human iPSCs are valuable tools for studying the mechanisms and developing novel therapeutic alternatives for Fabry disease.

Determination of Diversity, Distribution and Host Specificity of Korean Laccaria Using Four Approaches.

The genus Laccaria (Hydnangiaceae, Agaricales) plays an important role in forest ecosystems as an ectomycorrhizal fungus, contributing to nutrient cycles through symbiosis with many types of trees. Though understanding Laccaria diversity and distribution patterns, as well as its association with host plants, is fundamental to constructing a balanced plant diversity and conducting effective forest management, previous studies have not been effective in accurately investigating, as they relied heavily on specimen collection alone. To investigate the true diversity and distribution pattern of Laccaria species and determine their host types, we used four different approaches: specimen-based analysis, open database search (ODS), NGS analysis, and species-specific PCR (SSP). As a result, 14 Laccaria species have been confirmed in Korea. Results regarding the species distribution pattern were different between specimen-based analysis and SSP. However, when both were integrated, the exact distribution pattern of each Laccaria species was determined. In addition, the SSP revealed that many Laccaria species have a wide range of host types. This study shows that using these four different approaches is useful in determining the diversity, distribution, and host of ECM fungi. Furthermore, results obtained for Laccaria will serve as a baseline to help understand the role of ECM fungi in forest management in response to climate change.

Two New Species of Laccaria (Agaricales, Basidiomycota) from Korea.

Species of Laccaria (Hydnangiaceae, Agaricales, and Basidiomycota) are well-known ectomycorrhizal symbionts of a broad range of hosts. Laccaria species are characterized by brown, orange, or purple colored basidiocarps, and globose or oblong, echinulate and multinucleate basidiospores. While some Laccaria species are easily identified at the species level using only the morphological characteristics, others are hard to distinguish at the species level due to small differences in morphology. Heretofore, ten Laccaria species have been reported in Korea. While studying the fungal diversity in the National Parks of Korea, two new Laccaria species were discovered. Species identification was done based on molecular analyses (ITS, 28S rDNA, rpb2, and tef1), then were confirmed by their corresponding morphologies. The two newly discovered Laccaria species are proposed here as Laccaria macrobasidia and Laccaria griseolilacina. The unique morphological characters of L. macrobasidia that distinguish it from its closely related species are orange-brown colored basidiocarp, long basidia and the absence of cheilocystidia. L. griseolilacina is characterized by a light grayish lavender-colored pileus and the absence of cheilocystidia. Two new species are described and illustrated in the present paper.

How to Incorporate the Experiential Student Pharmacist Into the Pediatric Practice Setting.

Experiential education conducted in the pediatric practice setting provides student pharmacists the opportunity to learn about a unique patient population. For many students, experiential rotations may be the only form of pediatric education they receive in pharmacy school. Providing quality pediatric experiences is essential to stimulate students' interest in this practice area and train those with goals to become pediatric pharmacists. It is also important to ensure graduating pharmacists have exposure to fundamental pediatric pharmacy concepts. Although pediatric practice areas and institutions differ in patient populations and services, a well-rounded rotation experience should be provided for the pharmacy student. Preceptors must decide what concepts to teach and what activities students should be incorporated into during this experiential period. This article provides goals and activities for student pharmacists that can be included in newly designed introductory pharmacy practice experiences and advanced pharmacy practice experiences within various pediatric settings.

Bakkenolides and Caffeoylquinic Acids from the Aerial Portion of Petasites japonicus and Their Bacterial Neuraminidase Inhibition Ability.

Petasites japonicus have been used since a long time in folk medicine to treat diseases including plague, pestilential fever, allergy, and inflammation in East Asia and European countries. Bioactive compounds that may prevent and treat infectious diseases are identified based on their ability to inhibit bacterial neuraminidase (NA). We aimed to isolate and identify bioactive compounds from leaves and stems of P. japonicas (PJA) and elucidate their mechanisms of NA inhibition. Key bioactive compounds of PJA responsible for NA inhibition were isolated using column chromatography, their chemical structures revealed using 1 H NMR, 13 C NMR, DEPT, and HMBC, and identified to be bakkenolide B (1), bakkenolide D (2), 1,5-di-O-caffeoylquinic acid (3), and 5-O-caffeoylquinic acid (4). Of these, 3 exhibited the most potent NA inhibitory activity (IC50 = 2.3 ± 0.4 µM). Enzyme kinetic studies revealed that 3 and 4 were competitive inhibitors, whereas 2 exhibited non-competitive inhibition. Furthermore, a molecular docking simulation revealed the binding affinity of these compounds to NA and their mechanism of inhibition. Negative-binding energies indicated high proximity of these compounds to the active site and allosteric sites of NA. Therefore, PJA has the potential to be further developed as an antibacterial agent for use against diseases associated with NA.

Seventeen Unrecorded Species from Gayasan National Park in Korea.

Macrofungi play important roles in forest ecology as wood decayers, symbionts, and pathogens of living trees. For the effective forest management, it is imperative to have a comprehensive overview of macrofungi diversity in specific areas. As a part of the National Institute of Biological Resources projects for discovering indigenous fungi in Korea, we collected macrofungi in Gayasan National Park from 2017 to 2018. These specimens were identified based on morphological characteristics and sequence analysis of internal transcribed spacer (ITS) or the nuclear large subunit rRNA (LSU) region. We discovered 17 macrofungi new to Korea: Butyrea japonica, Ceriporia nanlingensis, Coltricia weii, Coltriciella subglobosa, Crepidotus crocophyllus, Cylindrobasidium laeve, Fulvoderma scaurum, Laetiporus cremeiporus, Lentinellus castoreus, Leucogyrophana mollusca, Marasmius insolitus, Nidularia deformis, Phaeophlebiopsis peniophoroides, Phanerochaete angustocystidiata, Phlebiopsis pilatii, Postia coeruleivirens, and Tengioboletus fujianensis. We described their detailed morphological characteristics.

Macrolepiota in Korea: New Records and a New Species.

The genus Macrolepiota (Agaricales, Basidiomycota) is easy to recognize at the genus level because of big, fleshy basidiocarps with squamules covering the pileus; a single or double annulus; and big, thick-walled basidiospores with a germ pore. However, morphological identification is often unreliable in Macrolepiota due to similar morphological features among species. Due to the uncertainty of previous morphological identification in the genus Macrolepiota, it is necessary to re-examine Korean Macrolepiota using molecular data. We re-examined 34 Macrolepiota specimens collected from 2012 to 2018 in Korea using a reverse taxonomic approach, whereby species identification was first done based on the internal transcribed spacer (ITS) region analysis, followed by morphological confirmation. We identified the presence of four species: M. detersa, M. mastoidea, M. procera, and M. umbonata sp. nov. Two species (M. detersa and M. mastoidea) were previously unrecorded from Korea and M. umbonata is a new species. Detailed descriptions of all four species and taxonomic key are provided in this study. Macrolepiota procera and M. umbonata are distributed through the country, but M. detersa and M. mastoidea are distributed only in limited areas. According to our results, the combination of ITS locus and morphology proved to be a robust approach to evaluate the taxonomic status of Macrolepiota species in Korea. Additional surveys are needed to verify the species diversity and clarify their geographic distribution.

Diversity and effect of Trichoderma isolated from the roots of Pinus densiflora within the fairy ring of pine mushroom (Tricholoma matsutake).

Pine mushroom (PM, Tricholoma matsutake) is an important ectomycorrhizal fungus in Asia primarily due to its value as a food delicacy. Recent studies have shown that fairy rings of PM have distinctive fungal communities, which suggests that other fungi influence the growth of PM. Trichoderma is a well-known saprotrophic fungus commonly found in pine roots within PM fairy rings; however, little is known about the diversity of Trichoderma associated with PM and how these species influence PM growth. This study focused on diversity of Trichoderma isolated from pine roots within PM fairy rings and how these species affect the growth of PM isolate. Based on tef1a phylogenetic analyses, nine Trichoderma species (261 isolates) were identified. Trichoderma songyi and T. spirale were the dominant species, and Trichoderma community varied geographically. Growth experiments indicated that metabolites from five Trichoderma species had a significant influence on the growth of PM isolates. Metabolites of two Trichoderma species increased PM growth, while those of three Trichoderma species suppressed the growth. Within the fairy rings, Trichoderma that had a positive or neutral effect comprised the majority of Trichoderma communities. The results of this study suggest that various Trichoderma species co-exist within PM fairy rings and that these species influence PM growth.

Guild Patterns of Basidiomycetes Community Associated With Quercus mongolica in Mt. Jeombong, Republic of Korea.

Depending on the mode of nutrition exploitation, major fungal guilds are distinguished as ectomycorrhizal and saprotrophic fungi. It is generally known that diverse environmental factors influence fungal communities; however, it is unclear how fungal communities respond differently to environment factors depend on fungal guilds. In this study, we investigated basidiomycetes communities associated with Quercus mongolica using 454 pyrosequencing. We attempted to detect guild pattern (ectomycorrhizal or saprotrophic fungal communities) by comparing the influence of geography and source (root and surrounding soil). A total of 515 mOTUs were detected from root (321) and soil (394) of Q. mongolica at three sites of Mt. Jeombong in Inje County. We found that patterns of diversity and community structure were different depending on the guilds. In terms of alpha diversity, only ectomycorrhizal fungi showed significant differences between sources. In terms of community structure, however, geography significantly influenced the ectomycorrhizal community, while source appeared to have a greater influence on the saprotrophic community. Therefore, a guild-based view will help to elucidates novel features of the relationship between environmental factors and fungal communities.

A systematic revision of the ectomycorrhizal genus Laccaria from Korea.

Species of Laccaria (Hydnangiaceae, Basidiomycota) are important in forest ecosystems as ectomycorrhizal fungi. Nine of the 75 described Laccaria species worldwide been reported from Korea. Most of these have European and North American names, and their identities are based solely on morphological features. To evaluate the taxonomy of Korean Laccaria, we used 443 specimens collected between 1981 and 2016 in a phylogenetic analysis based on sequence data from nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) region, nuc 28S rDNA (28S), RNA polymerase II subunit 2 (rpb2), and translation elongation factor 1-α (tef1). Ten Laccaria species were identified. Three of these were previously reported from Korea: L. bicolor, L. tortilis, and L. vinaceoavellanea. Laccaria alba, L. japonica, and L. murina are confirmed as new reports from Korea. Lastly, four new Laccaria species are described: L. araneosa, L. parva, L. torosa, and L. versiforma. This study supports the general contention that Asian species of ectomycorrhizal fungi may not be conspecific with morphologically similar species from Europe and North America. Furthermore, identification based on morphology alone is often unreliable in Laccaria due to considerable overlap of characters among species. Thus, use of molecular methods is necessary for effective identification. Illustrations of the four newly described species and a taxonomic key to species of Laccaria in Korea are provided.

Three New Recorded Species of the Physalacriaceae on Ulleung Island, Korea.

Most known species in the Physalacriaceae are saprotrophs that grow on decaying leaves and wood, and approximately 21 genera in the Physalacriaceae have been reported worldwide. During an ongoing survey of indigenous fungi in Korea, four specimens belonging to the Physalacriaceae were collected on Ulleung Island. These specimens were identified as three species based on morphological characteristics and molecular analysis of rDNA-internal transcribed spacer sequences. Three species in three genera were shown to be new records in Korea: Hymenopellis orientalis, Paraxerula hongoi, and Ponticulomyces orientalis. The latter two are the first records of these genera in Korea. In this study, we provide detailed morphological descriptions of these species and describe their phylogenetic position within the Physalacriaceae.

Ten New Recorded Species of Macrofungi on Ulleung Island, Korea.

Ulleung Island is a biodiversity hotspot in South Korea. During a survey of indigenous fungal species from Ulleung Island conducted from 2015 to 2016, we discovered 10 unrecorded macrofungi in Korea. These macrofungi were identified to the species level using morphological features and phylogenetic analysis based on the internal transcribed spacer region: Deconica phyllogena, Mycena zephirus, Phaeomarasmius proximans, Phlebia radiata, Pluteus semibulbosus, Postia alni, Resinicium pinicola, Scytinostroma portentosum, Tricholomopsis flammula, and Tyromyces kmetii. We also provide detailed morphological descriptions for these 10 species.

Seven New Recorded Species in Five Genera of the Strophariaceae in Korea.

Most known species in the Strophariaceae are decomposers and grow on various kind of organic matter. Approximately 18 genera and 1,316 species in the Strophariaceae have been reported worldwide. Through an ongoing survey of indigenous fungi in Korea, 29 specimens belonging to the Strophariaceae were collected from 2012 to 2016. These specimens were identified based on morphological characteristics and molecular analysis of internal transcribed spacer sequences. Fifteen taxa were confirmed, with eight species matching those previously recorded. Seven species in five genera were shown to be new records in Korea: Galerina marginata, Gymnopilus crociphyllus, Gymnopilus picreus, Hebeloma birrus, Hebeloma cavipes, Pholiota multicingulata, and Psilocybe thaizapoteca. In this study, we provide detailed morphological descriptions of these species and investigate their evolutionary relationships by constructing phylogenetic trees.