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https://www.readbyqxmd.com/read/29753128/selenate-sensitivity-of-a-laea-mutant-is-restored-by-overexpression-of-the-bzip-protein-metr-in-aspergillus-fumigatus
#1
Sachin Jain, Relebohile Sekonyela, Ben Knox, Jonathan M Palmer, Anna Huttenlocher, Mehdi Kabbage, Nancy P Keller
LaeA is a conserved global regulator of secondary metabolism and development in filamentous fungi. Examination of Aspergillus fumigatus transcriptome data of laeA deletion mutants have been fruitful in identifying genes and molecules contributing to the laeA mutant phenotype. One of the genes significantly down regulated in A. fumigatus ΔlaeA is metR, encoding a bZIP DNA binding protein required for sulfur and methionine metabolism in fungi. LaeA and MetR deletion mutants exhibit several similarities including down regulation of sulfur assimilation and methionine metabolism genes and ability to grow on the toxic sulfur analog, sodium selenate...
May 9, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29712727/the-human-cathelicidin-antimicrobial-peptide-ll-37-promotes-the-growth-of-the-pulmonary-pathogen-aspergillus-fumigatus
#2
Gerard Sheehan, Gudmundur Bergsson, Noel G McElvaney, Emer P Reeves, Kevin Kavanagh
The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the cathelicidin antimicrobial peptide LL-37 and the aim of this work was to assess the effect of LL-37 on the growth of Aspergillus fumigatus , a common pathogen of CF patients. Exposure of A. fumigatus to LL-37 and its derived fragment RK-31 (1.95 μg/ml) for 24 hours had a positive effect on growth (199.94 ± 6.172%, p < 0.05) and (218.20 ± 4.63%, p < 0.05) respectively, whereas scrambled LL-37 peptide did not (85.12 ± 2...
April 30, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29602047/molecular-characterization-of-aspergillus-fumigatus-isolated-from-raw-cow-milk-in-argentina-molecular-typing-of-a-fumigatus-from-raw-cow-milk
#3
Gabriela A Pena, Verónica Alonso, Marina Velasco Manini, M Pellegrino, Lilia R Cavaglieri
Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a gliotoxinogenic species into section Fumigati commonly found in contaminated animal environments. In dairy herds, exposed areas of lactating cows, as mammalian glandule, can be easily contaminated by them. This study was aimed to identify A. fumigatus sensu lato strains (identified based on morphology) isolated from raw cow milk at species level, by morphological and molecular techniques, and to estimate their genetic variability...
March 24, 2018: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29595339/antifeedant-activity-of-long-chain-alcohols-and-fungal-and-plant-metabolites-against-pea-aphid-acyrthosiphon-pisum-as-potential-biocontrol-strategy
#4
Thaïs Aznar-Fernández, Alessio Cimmino, Marco Masi, Diego Rubiales, Antonio Evidente
Aphids are noxious insect pests of major crops including cereals and legumes. Particularly, pea aphid (Acyrthosiphon pisum) causes significant yield and quality loses in pea. Crop protection is largely based on noxious chemical pesticides which have prompted a renewed interest in the discovery of natural products as alternatives to synthetic insecticides. In this study different classes of natural compounds were tested in dual choice bioassays to evaluate their feeding deterrence and mortality effect on pea aphid...
March 29, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29584673/effects-of-the-combination-of-gliotoxin-and-adriamycin-on-the-adriamycin-resistant-non-small-cell-lung-cancer-a549-cell-line
#5
Le Van Manh Hung, Yeon Woo Song, Somi Kim Cho
Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and the search for effective compounds against resistant cancer is still advancing. Marine organisms are a promising natural resource for the discovery and development of anticancer agents. In this study, we examined whether gliotoxin (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus , inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via fluorescence-activated cell sorting analysis, Hoechst staining, annexin V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and western blotting...
March 27, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29577474/prospective-evaluation-of-a-combination-of-fungal-biomarkers-for-the-diagnosis-of-invasive-fungal-disease-in-high-risk-hematology-patients
#6
Helena Hammarström, Anna Stjärne Aspelund, Bertil Christensson, Claus Peter Heußel, Jenny Isaksson, Nahid Kondori, Lennart Larsson, Pawel Markowicz, Johan Richter, Christine Wennerås, Vanda Friman
We prospectively evaluated a combination of fungal biomarkers in adult hematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once- to twice-weekly for serum (1-3)-ß-D-Glucan (BG), galactomannan (GM), bismethyl-gliotoxin and urinary D-arabinitol/L-arabinitol ratio. Thirteen cases with proven or probable IFD were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within two weeks from the TOD the sensitivity of BG was 92%...
March 25, 2018: Mycoses
https://www.readbyqxmd.com/read/29551195/dysregulated-gliotoxin-biosynthesis-attenuates-the-production-of-unrelated-biosynthetic-gene-cluster-encoded-metabolites-in-aspergillus-fumigatus
#7
Sean Doyle, Gary W Jones, Stephen K Dolan
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus. The gliotoxin bis-thiomethyltransferase, GtmA, attenuates gliotoxin biosynthesis in A. fumigatus by conversion of dithiol gliotoxin to bis-thiomethylgliotoxin (BmGT). Here we show that disruption of dithiol gliotoxin bis-thiomethylation functionality in A. fumigatus results in significant remodelling of the A...
April 2018: Fungal Biology
https://www.readbyqxmd.com/read/29393399/reduced-gliotoxin-induces-ros-mediated-anoikis-in-human-colorectal-cancer-cells
#8
Junxiong Chen, Qiong Lou, Lu He, Chuangyu Wen, Mengmeng Lin, Zefeng Zhu, Fang Wang, Lanlan Huang, Wenjian Lan, Aikichi Iwamoto, Xiangling Yang, Huanliang Liu
Reduced-gliotoxin is a small molecule derived from the secondary metabolites of marine fungi; compared to other gliotoxin analogues, it exhibits potent anticancer effects. However, the molecular basis of the death of colorectal cancer (CRC) cells induced by reduced-gliotoxin is unclear. Thus, the aim of this study was to investigate the potency of reduced-gliotoxin against CRC cells and to elucidate the underlying mechanisms. Cell morphology, flow cytometric analysis and western bolt analysis were performed to examine the functions and mechanisms of cell death induced by reduced-gliotoxin...
March 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29216817/characterization-of-sulfhydryl-oxidase-from-aspergillus-tubingensis
#9
Outi Nivala, Greta Faccio, Mikko Arvas, Perttu Permi, Johanna Buchert, Kristiina Kruus, Maija-Liisa Mattinen
BACKGROUND: Despite of the presence of sulfhydryl oxidases (SOXs) in the secretomes of industrially relevant organisms and their many potential applications, only few of these enzymes have been biochemically characterized. In addition, basic functions of most of the SOX enzymes reported so far are not fully understood. In particular, the physiological role of secreted fungal SOXs is unclear. RESULTS: The recently identified SOX from Aspergillus tubingensis (AtSOX) was produced, purified and characterized in the present work...
December 8, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/29203804/kif1b%C3%AE-increases-ros-to-mediate-apoptosis-and-reinforces-its-protein-expression-through-o-2-in-a-positive-feedback-mechanism-in-neuroblastoma
#10
Clara Angelina, Irene Sze Ying Tan, Zhang'e Choo, Oswald Zhao Jian Lee, Shazib Pervaiz, Zhi Xiong Chen
Relapse-prone, poor prognosis neuroblastoma is frequently characterized by deletion of chr1p36 where tumor suppressor gene KIF1Bβ resides. Interestingly, many 1p36-positive patients failed to express KIF1Bβ protein. Since altered cellular redox status has been reported to be involved in cell death and protein modification, we investigated the relationship between reactive oxygen species (ROS) and KIF1Bβ. Here, we showed that wild-type KIF1Bβ protein expression positively correlates with superoxide (O2 - ) and total ROS levels in neuroblastoma cells, unlike apoptotic loss-of-function KIF1Bβ mutants...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149178/drivers-of-genetic-diversity-in-secondary-metabolic-gene-clusters-within-a-fungal-species
#11
Abigail L Lind, Jennifer H Wisecaver, Catarina Lameiras, Philipp Wiemann, Jonathan M Palmer, Nancy P Keller, Fernando Rodrigues, Gustavo H Goldman, Antonis Rokas
Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence...
November 2017: PLoS Biology
https://www.readbyqxmd.com/read/29123130/binding-of-mycotoxins-to-proteins-involved-in-neuronal-plasticity-a-combined-in-silico-wet-investigation
#12
Bernardina Scafuri, Antonio Varriale, Angelo Facchiano, Sabato D'Auria, Maria Elisabetta Raggi, Anna Marabotti
We have applied a combined computational procedure based on inverse and direct docking in order to identify putative protein targets of a panel of mycotoxins and xenobiotic compounds that can contaminate food and that are known to have several detrimental effects on human health. This procedure allowed us to identify a panel of human proteins as possible targets for aflatoxins, gliotoxin, ochratoxin A and deoxynivalenol. Steady-state fluorescence and microscale thermophoresis experiments allowed us to confirm the binding of some of these mycotoxins to acetylcholinesterase and X-linked neuroligin 4, two proteins involved in synapse activity and, particularly for the second protein, neuronal plasticity and development...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109714/characteristics-of-a-regulator-of-g-protein-signaling-rgs-rgsc-in-aspergillus-fumigatus
#13
Young Kim, In-Beom Heo, Jae-Hyuk Yu, Kwang-Soo Shin
The regulator of G-protein signaling (RGS) proteins have a conserved RGS domain that facilitates the intrinsic GTPase activity of an activated Gα subunit of heterotrimeric G protein, thereby attenuating signal transduction. Among six predicted RGS proteins in the opportunistic human pathogenic fungus Aspergillus fumigatus , only three (FlbA, GprK, and Rax1) have been studied. The unexplored RgsC composed of the Phox-associated (PXA), RGS, Phox homology (PX), and Nexin_C superfamily domains is highly conserved in many ascomycete fungi, suggesting a crucial role of RgsC in fungal biology...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29109676/oxytocin-removes-estrous-female-vs-male-preference-of-virgin-male-rats-mediation-of-the-supraoptic-nucleus-via-olfactory-bulbs
#14
Xiao-Yu Liu, Dan Cui, Dongyang Li, Runsheng Jiao, Xiaoran Wang, Shuwei Jia, Dan Hou, Tong Li, Haitao Liu, Ping Wang, Yu-Feng Wang
Social functions of oxytocin (OT) have been explored extensively; however, relationship between the effect of intranasally applied OT (nasal OT) on the social preference (SP) and intracerebral actions of endogenous OT remains unclear. To resolve this question, we first observed effects of nasal OT on the SP of virgin young adult male rats toward unfamiliar virgin estrous female (EF) vs. virgin male rats. The results showed that the test male rats exhibited significantly more times and longer duration accessing the female than the male, which were acutely eliminated by nasal OT...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29036999/-the-contamination-and-dietary-exposure-analysis-for-seven-mycotoxins-in-the-fifth-chinese-total-diet-study
#15
N N Qiu, B Lyu, S Zhou, Y F Zhao, Y N Wu
Objective: To investigate the contamination levels and dietary intakes of seven mycotoxins in Chinese diets. Methods: In Chinese Total Diet Study, food aggregation was based on the food consumption of local residents, thus generating the sampling scheme. According to the sampling scheme, the food items were sampled at three survey points in each province and then mixed in the same proportion. The mixed dietary samples were prepared after being cooked and processed. The samples comprised of 13 categories of food: cereals, beans, potatoes, meat, eggs, aquatic products, milk, vegetables, fruits, saccharides, beverages and drinking water, alcohol, and condiments...
October 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28966975/nongenomic-glucocorticoid-suppression-of-a-postsynaptic-potassium-current-via-emergent-autocrine-endocannabinoid-signaling-in-hypothalamic-neuroendocrine-cells-following-chronic-dehydration
#16
Ning Wu, Jeffrey G Tasker
Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (IA), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent IA...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28887465/host-immune-status-specific-production-of-gliotoxin-and-bis-methyl-gliotoxin-during-invasive-aspergillosis-in-mice
#17
Janyce A Sugui, Stacey R Rose, Glenn Nardone, Muthulekha Swamydas, Chyi-Chia R Lee, Kyung J Kwon-Chung, Michail S Lionakis
Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT's role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795659/role-of-mycotoxins-in-the-pathobiology-of-autism-a-first-evidence
#18
Barbara De Santis, Carlo Brera, Alessandra Mezzelani, Sabina Soricelli, Francesca Ciceri, Giorgio Moretti, Francesca Debegnach, Maria Clara Bonaglia, Laura Villa, Massimo Molteni, Maria Elisabetta Raggi
OBJECTIVES: Gene-environment interaction is an emerging hypothesis to expound not only the autism pathogenesis but also the increased incidence of neurodevelopmental disorders (such as autistic spectrum disorder, attention-deficit, hyperactivity disorder). Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism, try to explain their mechanism of action, and discuss possible preventive and therapeutic interventions...
August 10, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28762595/perinatal-high-fat-diet-increases-inhibition-of-dorsal-motor-nucleus-of-the-vagus-neurons-regulating-gastric-functions
#19
C A McMenamin, R A Travagli, K N Browning
BACKGROUND: Previous studies suggest an increased inhibition of dorsal motor nucleus of the vagus (DMV) neurons following exposure to a perinatal high fat diet (PNHFD); the underlying neural mechanisms, however, remain unknown. This study assessed the effects of PNHFD on inhibitory synaptic inputs to DMV neurons and the vagally dependent control of gastric tone and motility. METHODS: Whole-cell patch clamp recordings were made from DMV neurons in thin brainstem slices from Sprague-Dawley rats fed either a control diet or HFD (14 or 60% kcal from fat, respectively) from embryonic day 13 onwards; gastric tone and motility were recorded in in vivo anesthetized rats...
January 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28736522/gliotoxin-targets-nuclear-notch2-in-human-solid-tumor-derived-cell-lines-in-vitro-and-inhibits-melanoma-growth-in-xenograft-mouse-model
#20
Rainer Hubmann, Wolfgang Sieghart, Susanne Schnabl, Mohammad Araghi, Martin Hilgarth, Marlies Reiter, Dita Demirtas, Peter Valent, Christoph Zielinski, Ulrich Jäger, Medhat Shehata
Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT...
2017: Frontiers in Pharmacology
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