Evolution of the Toxins Muscarine and Psilocybin in a Family of Mushroom-Forming Fungi

Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10–20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa. DOI: 10.1371/journal.pone.006464

Evolution of the Toxins Muscarine and Psilocybin in a Family of Mushroom-Forming Fungi

Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10–20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa. DOI: 10.1371/journal.pone.006464

Quorum Sensing Signal Production and Microbial Interactions in a Polymicrobial Disease of Corals and the Coral Surface Mucopolysaccharide Layer

Black band disease (BBD) of corals is a complex polymicrobial disease considered to be a threat to coral reef health, as it can lead to mortality of massive reef-building corals. The BBD community is dominated by gliding, filamentous cyanobacteria with a highly diverse population of heterotrophic bacteria. Microbial interactions such as quorum sensing (QS) and antimicrobial production may be involved in BBD disease pathogenesis. In this study, BBD (whole community) samples, as well as 199 bacterial isolates from BBD, the surface mucopolysaccharide layer (SML) of apparently healthy corals, and SML of apparently healthy areas of BBD-infected corals were screened for the production of acyl homoserine lactones (AHLs) and for autoinducer-2 (AI-2) activity using three bacterial reporter strains. AHLs were detected in all BBD (intact community) samples tested and in cultures of 5.5% of BBD bacterial isolates. Over half of a subset (153) of the isolates were positive for AI-2 activity. AHL-producing isolates were further analyzed using LC-MS/MS to determine AHL chemical structure and the concentration of (S)-4,5-dihydroxy-2,3-pentanedione (DPD), the biosynthetic precursor of AI-2. C6-HSL was the most common AHL variant detected, followed by 3OC4-HSL. In addition to QS assays, 342 growth challenges were conducted among a subset of the isolates, with 27% of isolates eliciting growth inhibition and 2% growth stimulation. 24% of BBD isolates elicited growth inhibition as compared to 26% and 32% of the bacteria from the two SML sources. With one exception, only isolates that exhibited AI-2 activity or produced DPD inhibited growth of test strains. These findings demonstrate for the first time that AHLs are present in an active coral disease. It is possible that AI-2 production among BBD and coral SML bacteria may structure the microbial communities of both a polymicrobial infection and the healthy coral microbiome

Thiobenzothiazole-modified hydrocortisones display anti-inflammatory activity with reduced impact on islet β-cell function

© 2015, American Society for Biochemistry and Molecular Biology Inc. All rights reserved. Glucocorticoids signal through the glucocorticoid receptor (GR) and are administered clinically for a variety of situations, including inflammatory disorders, specific cancers, rheumatoid arthritis, and organ/tissue transplantation. However, glucocorticoid therapy is also associated with additional complications, including steroid-induced diabetes. We hypothesized that modification of the steroid backbone is one strategy to enhance the therapeutic potential of GR activation. Toward this goal, two commercially unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent and human islets. We found that MS4 had transrepression properties but lacked transactivation ability, whereas MS6 retained both transactivation and transrepression activities. In addition, MS4 and MS6 both displayed anti-inflammatory activity. Furthermore, MS4 displayed reduced impact on islet β-cell function in both rodent and human islets. Similar to dexamethasone, MS6 promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We conclude that modification of the functional groups attached to the D-ring of the hydrocortisone steroid molecule produces compounds with altered structure-function GR agonist activity with decreased impact on insulin secretion and reduced adipogenic potential but with preservation of anti-inflammatory activity

Current State of Conservation Knowledge on Threatened Amphibian Species in Peru

This study documents the current state of conservation knowledge on threatened amphibian species in Peru. Following the International Union for the Conservation of Nature (IUCN) classification system, we considered species in the following categories: Critically Endangered, Endangered, Vulnerable, and Near Threatened. Even though only the first three categories are regarded as threatened by IUCN, we included the fourth category to make comparisons with the list of threatened species issued by the Peruvian government. We used the Global Amphibian Assessment\u27s database and the list issued in Peru for this comparison. We conducted separate field surveys in 17 regions of Peru to evaluate the presence/absence of threatened amphibian species and species that are potentially threatened. We also used the Declining Amphibian Database-DAPTF, to compare our results with previous assessments on population declines, and the World Wildlife Fund\u27s Wildfinder database, to determine in which Neotropical ecoregion each species occurs. We compiled data on 83 species, 44 of which are recognized as threatened by the IUCN and/or the Peruvian government. The remaining 39 species should be re-assessed as they face various threats. A re-evaluation of current estimates is needed as only 8% of all species recorded in Peru are recognized as threatened by the government, whereas the global estimate of threatened species is about 32%. In addition to using IUCN criteria, this re-assessment should follow national guidelines standardized in Peru and be in accordance with the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Because the habitat of almost 40% of threatened species reported herein still remains unprotected, and data on chytridiomycosis and other threats are lacking for most taxa, it is crucial to develop strategies for habitat conservation and research on disease dynamics in natural populations

Treatment Burden and Chronic Illness: Who is at Most Risk?

Background: There is a need to ascertain the type and level of treatment burden experienced by people with co-morbidities. This is important to identify the characteristics of participants who are at most risk of treatment burden.  Objective: The aim of this study is to identify the characteristics of participants who are at most risk of treatment burden.  Methods: This cross-sectional study was part of a larger project and recruitment was conducted across four Australian regions: rural, semi-rural and metropolitan. Participants were asked about their treatment burden using an adapted version of a measure, which included the following five dimensions: medication, time and administrative, lifestyle change, social life and financial burden.  Results: In total, 581 participants with various chronic health conditions reported a mean global treatment burden of 56.5 out of 150 (standard deviation = 34.5). Number of chronic conditions (β = .34, p < 0.01), age, (β = −.27, p < 0.01), the presence of an unpaid carer (β = .22, p < 0.001) and the presence of diabetes mellitus and other endocrine conditions (β = .13, p < 0.01) were significant predictors of overall treatment burden. For the five dimensions of treatment burden, social, medicine and administrative burden were predicted by the same cluster of variables: number of conditions, age, presence of an unpaid carer and diabetes. However, in addition to these variables, financial dimensions were also predicted by education level, ethnicity and health insurance. Educational level also influenced lifestyle burden.  Conclusion: A substantial proportion of community-dwelling adults with chronic conditions have considerable levels of treatment burden. Specifically, health professionals should provide greater focus on managing overall treatment burden for persons who are of young age, have an endocrine condition or an unpaid carer, or a combination of these factors

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

What Do the First 597 Global Fungal Red List Assessments Tell Us about the Threat Status of Fungi?

Fungal species are not immune to the threats facing animals and plants and are thus also prone to extinction. Yet, until 2015, fungi were nearly absent on the IUCN Red List. Recent efforts to identify fungal species under threat have significantly increased the number of published fungal assessments. The 597 species of fungi published in the 2022-1 IUCN Red List update (21 July 2022) are the basis for the first global review of the extinction risk of fungi and the threats they face. Nearly 50% of the assessed species are threatened, with 10% NT and 9% DD. For regions with a larger number of assessments (i.e., Europe, North America, and South America), subanalyses are provided. Data for lichenized and nonlichenized fungi are also summarized separately. Habitat loss/degradation followed by climate change, invasive species, and pollution are the primary identified threats. Bias in the data is discussed along with knowledge gaps. Suggested actions to address these gaps are provided along with a discussion of the use of assessments to facilitate on-the-ground conservation efforts. A research agenda for conservation mycology to assist in the assessment process and implementation of effective species/habitat management is presented

What Do the First 597 Global Fungal Red List Assessments Tell Us about the Threat Status of Fungi?

Fungal species are not immune to the threats facing animals and plants and are thus also prone to extinction. Yet, until 2015, fungi were nearly absent on the IUCN Red List. Recent efforts to identify fungal species under threat have significantly increased the number of published fungal assessments. The 597 species of fungi published in the 2022-1 IUCN Red List update (21 July 2022) are the basis for the first global review of the extinction risk of fungi and the threats they face. Nearly 50% of the assessed species are threatened, with 10% NT and 9% DD. For regions with a larger number of assessments (i.e., Europe, North America, and South America), subanalyses are provided. Data for lichenized and nonlichenized fungi are also summarized separately. Habitat loss/degradation followed by climate change, invasive species, and pollution are the primary identified threats. Bias in the data is discussed along with knowledge gaps. Suggested actions to address these gaps are provided along with a discussion of the use of assessments to facilitate on-the-ground conservation efforts. A research agenda for conservation mycology to assist in the assessment process and implementation of effective species/habitat management is presented