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https://www.readbyqxmd.com/read/28476772/biosynthesis-of-the-pharmaceutically-important-fungal-ergot-alkaloid-dihydrolysergic-acid-requires-a-specialized-allele-of-cloa
#1
Stephanie L Arnold, Daniel G Panaccione
Ergot alkaloids are fungal specialized metabolites that are important as the bases of several pharmaceuticals. Many ergot alkaloids are derivatives of lysergic acid (LA) and have vasoconstrictive activity, whereas several dihydrolysergic acid (DHLA) derivatives are vasorelaxant. The pathway to LA is established, with the P450 monooxygenase CloA playing a key role in oxidizing its substrate agroclavine to LA. We analyzed the activities of products of cloA alleles from different fungi relative to DHLA biosynthesis by expressing them in a mutant of the fungus Neosartorya fumigata that accumulates festuclavine, the precursor to DHLA...
May 5, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28452203/brachypodium-distachyon-as-alternative-model-host-system-for-the-ergot-fungus-claviceps-purpurea
#2
Sabine Kind, Selma Schurack, Janine Hinsch, Paul Tudzynski
To investigate its susceptibility to ergot infection we inoculated Brachypodium distachyon with Claviceps purpurea and compared the infection symptoms to those on rye (Secale cereale). We showed that after inoculation of Brachypodium with Claviceps the same disease symptoms occurred in comparable temporal and spatial patterns as on rye. The infection rate of Claviceps on this host is reduced compared to rye, but the disease can be surveyed by fungal gDNA quantification. Mutants of Claviceps which are virulence-attenuated on rye were also affected on Brachypodium...
April 27, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28428084/metabolomics-of-fescue-toxicosis-in-grazing-beef-steers
#3
Ryan S Mote, Nicholas S Hill, Karan Uppal, ViLinh T Tran, Dean P Jones, Nikolay M Filipov
Fescue toxicosis (FT) results from consumption of tall fescue (Lolium arundinaceum) infected with an endophyte (Epichloë coenophiala) that produces ergot alkaloids (EA), which are considered key etiological agents of FT. Decreased weight gains, hormonal imbalance, circulating cholesterol disruption, and decreased volatile fatty acid absorption suggest toxic (E+) fescue-induced metabolic perturbations. Employing untargeted high-resolution metabolomics (HRM) to analyze E+ grazing-induced plasma and urine metabolome changes, fescue-naïve Angus steers were placed on E+ or non-toxic (Max-Q) fescue pastures and plasma and urine were sampled before, 1, 2, 14, and 28 days after pasture assignment...
April 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28425871/the-journey-of-the-non-vascular-relief-for-migraine-from-triptans-to-ditans
#4
Alphienes Stanley Xavier, Mageshwaran Lakshmanan, Vikneswaran Gunaseelan
Migraine is a recurrent, disabling, complex and highly prevalent neurological disorder. The mystery behind the cause of migraine is continuously evolving, according to the scientific understanding of the disease. This growing understanding helps to identify novel therapeutic targets for the management of migraine to treat the ailing migraineurs. The role of serotonin (5HT) in migraine is recognized to be the cornerstone for the currently available therapeutic options namely ergot alkaloids and triptans. The role of mediators such as Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory neurotransmitter glutamate, has been realized and ignited the development of drugs targeting these factors...
April 19, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28392308/effects-of-grazing-tall-fescue-containing-ergot-alkaloids-on-bull-sperm-cryopreservation
#5
C R Burnett, W C Bridges, S L Pratt
There are many positive agronomic traits that make tall fescue a desirable forage, however, reduced fertility rates are reported for beef cattle grazing pasture containing the ergot alkaloid-producing endophyte, Epichloë coenophiala. The objective of this study was to assess the influence of consuming tall fescue containing ergot alkaloids on sperm physiology, as measured by survival of sperm following cryopreservation. Yearling Angus bulls (n=25), having passed a breeding soundness exam (BSE), were assigned to one of two treatments accounting for body weight (BW) and body condition score (BCS)...
March 28, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28380578/ruminal-tryptophan-utilizing-bacteria-degrade-ergovaline-from-tall-fescue-seed-extract
#6
B E Harlow, J P Goodman, B C Lynn, M D Flythe, H Ji, G E Aiken
The objectives of this study were to evaluate degradation of ergovaline in a tall fescue [ (Schreb.) Darbysh.] seed extract by rumen microbiota ex vivo and to identify specific bacteria capable of ergovaline degradation in vitro. Rumen cell suspensions were prepared by harvesting rumen fluid from fistulated wether goats ( = 3), straining, and differential centrifugation. Suspensions were dispensed into anaerobic tubes with added Trypticase with or without extract (∼10 μg kg ergovaline). Suspensions were incubated for 48 h at 39°C...
February 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28375902/ergothioneine-antioxidant-function-from-chemistry-to-cardiovascular-therapeutic-potential
#7
Luigi Servillo, Nunzia DʼOnofrio, Maria Luisa Balestrieri
Ergothioneine (ESH), the betaine of 2-mercapto-L-histidine, is a water-soluble naturally occurring amino acid with antioxidant properties. ESH accumulates in several human and animal tissues up to millimolar concentration through its high affinity transporter, namely the organic cation transporter 1 (OCTN1). ESH, first isolated from the ergot fungus (Claviceps purpurea), is synthesized only by Actinomycetales and non-yeast-like fungi. Plants absorb ESH via symbiotic associations between their roots and soil fungi, whereas mammals acquire it solely from dietary sources...
April 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28372538/cross-talk-of-the-biotrophic-pathogen-claviceps-purpurea-and-its-host-secale-cereale
#8
Birgitt Oeser, Sabine Kind, Selma Schurack, Thomas Schmutzer, Paul Tudzynski, Janine Hinsch
BACKGROUND: The economically important Ergot fungus Claviceps purpurea is an interesting biotrophic model system because of its strict organ specificity (grass ovaries) and the lack of any detectable plant defense reactions. Though several virulence factors were identified, the exact infection mechanisms are unknown, e.g. how the fungus masks its attack and if the host detects the infection at all. RESULTS: We present a first dual transcriptome analysis using an RNA-Seq approach...
April 4, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28357872/enantioselective-total-synthesis-of-lysergol-a-formal-anti-carbopalladation-heck-cascade-as-the-key-step
#9
Bastian Milde, Martin Pawliczek, Peter G Jones, Daniel B Werz
The enantioselective synthesis of (+)-lysergol was completed in 12 steps and an overall yield of 13% starting from a known literature precursor. The key step relies on a domino reaction containing a formal anti-carbopalladation, which is terminated by a β-silyl-directed Heck reaction. During this transformation, the two six-membered rings of the ergot scaffold are formed in a completely stereospecific manner.
April 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28350362/ergot-alkaloids-in-fattening-chickens-broilers-toxic-effects-and-carry-over-depending-on-dietary-fat-proportion-and-supplementation-with-non-starch-polysaccharide-nsp-hydrolyzing-enzymes
#10
Sven Dänicke
Ergot alkaloids (EA) are mycotoxins produced by Claviceps purpurea. EA-toxicity is poorly characterized for fattening chickens. Therefore, a dose-response study was performed to identify the lowest, and no observed adverse effect levels (LOAEL and NOAEL, respectively) based on several endpoints. Non-starch-polysaccharide (NSP) cleaving enzyme addition and dietary fat content were additionally considered as factors potentially influencing EA-toxicity. Feed intake was proven to respond most sensitively to the EA presence in the diets...
March 28, 2017: Toxins
https://www.readbyqxmd.com/read/28332434/occurrence-of-ergot-alkaloids-in-wheat-from-albania
#11
Dritan Topi, Breda Jakovac-Strajn, Katarina Pavšič-Vrtač, Gabrijela Tavčar-Kalcher
In the present study, the occurrence of ergot alkaloids in wheat harvested in Albania was investigated. A total of 71 samples of winter wheat collected in the years 2014 and 2015 were analysed for the twelve most important ergot alkaloids using liquid chromatography-tandem mass spectrometry. In the harvesting year 2014, 48.6% of samples were contaminated with ergot alkaloids, whereas in 2015 only 19.4% of samples were contaminated. In 2014, the concentrations of total ergot alkaloids ranged from 17.3 to 975...
March 23, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/28300233/ergot-alkaloids-synthetic-approaches-to-lysergic-acid-and-clavine-alkaloids
#12
REVIEW
Haichao Liu, Yanxing Jia
Covering: 2000 to 2017Ergot alkaloids are among the most important pharmaceuticals and natural toxins. Significant progress has been achieved in recent years on the research of ergot alkaloids. In this review, we re-introduced the history of ergot alkaloids. Meanwhile, we summarized all the natural products and semi-synthetic derivatives of ergot alkaloids. We also briefly described the biosynthesis and semi-synthesis of ergot alkaloid drugs from raw materials obtained by fermentation. Moreover, we reviewed the advances that have been made in the total synthesis of ergot alkaloids since 2000...
April 5, 2017: Natural Product Reports
https://www.readbyqxmd.com/read/28277860/conservative-treatment-of-pelvic-congestion-syndrome-indications-and-opportunities
#13
S G Gavrilov, O O Turischeva
INTRODUCTION: This brief review describes conservative treatment methods for pelvic venous congestion. Therapy options: The authors present an analysis of the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), ergot alkaloid derivatives, hormonal agents, venoprotective agents, and compression therapy in the treatment of pelvic congestion syndrome (PCS) as well as indications for medical therapy. CONCLUSION: The paucity of studies addressing this topic and the need for large multidisciplinary studies to explore the opportunities for non-surgical treatment of PCS are highlighted...
June 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28257512/quantitative-molecular-diagnostic-assays-of-grain-washes-for-claviceps-purpurea-are-correlated-with-visual-determinations-of-ergot-contamination
#14
Alexia Comte, Tom Gräfenhan, Matthew G Links, Sean M Hemmingsen, Tim J Dumonceaux
We examined the epiphytic microbiome of cereal grain using the universal barcode chaperonin-60 (cpn60). Microbial community profiling of seed washes containing DNA extracts prepared from field-grown cereal grain detected sequences from a fungus identified only to Class Sordariomycetes. To identify the fungal sequence and to improve the reference database, we determined cpn60 sequences from field-collected and reference strains of the ergot fungus, Claviceps purpurea. These data allowed us to identify this fungal sequence as deriving from C...
2017: PloS One
https://www.readbyqxmd.com/read/28240164/effects-of-dietary-mycotoxins-on-gut-microbiome
#15
Kexin Du, C Wang, Ping Liu, Yuan Li, Xi Ma
The harmful effects of mycotoxins on intestinal health have received worldwide attention. Mycotoxins are toxic secondary metabolites produced by filamentous fungi, and include aflatoxins, ochratoxins, patulin, fumonisins, zearalenone, trichothecenes, and ergot alkaloids. Insuring the absence or low levels of mycotoxins is critical for food and feed safety. Currently, the studies in this field have illuminated the adverse effects of mycotoxins on gut health including intestinal integrity and the gut-associated immune system...
February 22, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28168931/ergot-alkaloids-of-the-family-clavicipitaceae
#16
Simona Florea, Daniel G Panaccione, Christopher L Schardl
Ergot alkaloids are highly diverse in structure, exhibit diverse effects on animals, and are produced by diverse fungi in the phylum Ascomycota, including pathogens and mutualistic symbionts of plants. These mycotoxins are best known from the fungal family Clavicipitaceae and are named for the ergot fungi that, through millennia, have contaminated grains and caused mass poisonings, with effects ranging from dry gangrene to convulsions and death. However, they are also useful sources of pharmaceuticals for a variety of medical purposes...
May 2017: Phytopathology
https://www.readbyqxmd.com/read/28107016/total-syntheses-of-hibiscone-c-and-lysergine-a-cyclization-fragmentation-strategy
#17
Yandong Lu, Haosen Yuan, Shijie Zhou, Tuoping Luo
The first asymmetric total synthesis of (-)-hibiscone C and a concise synthesis of ergot alkaloid lysergine are described. Both syntheses were achieved using the radical cyclization/fragmentation strategy. This cascade reaction enabled the application of the strained bicycle as a synthon for the synthesis of highly substituted decalins in an efficient and stereoselective manner.
January 20, 2017: Organic Letters
https://www.readbyqxmd.com/read/28106398/synthesis-of-lysergol-and-its-analogues-to-assess-serotonin-receptor-activity
#18
Haosen Yuan, Zhixian Guo, Tuoping Luo
An efficient synthesis of ergot alkaloid lysergol and its analogues is described, providing compounds for functional evaluation at the human 5-HT1A, 5-HT2A, 5-HT2B, or 5-HT2C receptors. Key features of the synthesis include the development of a tandem reaction to construct the multifunctionalized piperidine skeleton and use of a rhodium-catalyzed [3 + 2] annulation in the late-stage indole formation.
January 20, 2017: Organic Letters
https://www.readbyqxmd.com/read/28096656/analysis-of-pramipexole-dose-response-relationships-in-parkinson-s-disease
#19
Ying Wang, Sheng-Gang Sun, Sui-Qiang Zhu, Chun-Feng Liu, Yi-Ming Liu, Qing Di, Hui-Fang Shang, Yan Ren, Wei Xiang, Sheng-Di Chen
BACKGROUND: Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson's disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined. METHODS: Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson's Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28074041/transcription-factor-xpp1-is-a-switch-between-primary-and-secondary-fungal-metabolism
#20
Christian Derntl, Bernhard Kluger, Christoph Bueschl, Rainer Schuhmacher, Robert L Mach, Astrid R Mach-Aigner
Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei Xpp1 was previously described as a repressor of xylanases...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
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