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the first case of invasive mixed-mold infections due to emericella nidulans var. echinulata and rasamsonia piperina in a patient with chronic granulomatous disease.a 16-year-old boy with chronic granulomatous disease presented with pneumonia and rib osteomyelitis. emericella nidulans var. echinulata was isolated from his sputum. after starting voriconazole, rasamsonia piperina was isolated from the rib swelling. a combination therapy of voriconazole and micafungin effectively eradicated this invasive mixed-mold infection. in immunocompromised patients, a precise pathogenic diagnosis is clinically useful for administration of an appropriate treatment regime ...201626563166
structure of the dioxygenase asqj: mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis.multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. the fe(ii)/α-ketoglutarate-dependent dioxygenase asqj from aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6 ...201626553478
effect of biotransformation by liver s9 enzymes on the mutagenicity and cytotoxicity of melanin extracted from aspergillus nidulans.a mutant that exhibited increased melanin pigment production was isolated from aspergillus nidulans fungus. this pigment has aroused biotechnological interest due to its photoprotector and antioxidant properties. in a recent study, we showed that melanin from a. nidulans also inhibits no and tnf-α production.201626459656
small heat shock proteins, phylogeny in filamentous fungi and expression analyses in aspergillus nidulans.small heat shock proteins (shsps) have been characterized in organisms from all three domains of life and viruses and are involved in a wide range of biological functions. however, the evolution and function of shsp in aspergillus species are largely unknown. in the present work, shsps were identified in 31 filamentous fungi, including species from aspergillus, penicillium, fusarium and magnaporthe, as well as botrytis cinerea and neurospora crassa. phylogenetic analysis revealed high level of d ...201626403724
the aspergillus nidulans syntaxin pepa(pep12) is regulated by two sec1/munc-18 proteins to mediate fusion events at early endosomes, late endosomes and vacuoles.syntaxins are target-snares that crucially contribute to determine membrane compartment identity. three syntaxins, tlg2p, pep12p and vam3p, organize the yeast endovacuolar system. remarkably, filamentous fungi lack the equivalent of the yeast vacuolar syntaxin vam3p, making unclear how these organisms regulate vacuole fusion. we show that the nearly essential aspergillus nidulans syntaxin pepa(pep12) , present in all endocytic compartments between early endosomes and vacuoles, shares features of ...201626395371
seeing the world differently: variability in the photosensory mechanisms of two model fungi.light plays an important role for most organisms on this planet, serving either as a source of energy or information for the adaptation of biological processes to specific times of day. the fungal kingdom is estimated to contain well over a million species, possibly 10-fold more, and it is estimated that a majority of the fungi respond to light, eliciting changes in several physiological characteristics including pathogenesis, development and secondary metabolism. two model organisms for photobi ...201626373782
nitric oxide synthesis by nitrate reductase is regulated during development in aspergillus.nitric oxide (no) is a signalling molecule involved in many biological processes in bacteria, plants and mammals. however, little is known about the role and biosynthesis of no in fungi. here we show that no production is increased at the early stages of the transition from vegetative growth to development in aspergillus nidulans. full no production requires a functional nitrate reductase (nr) gene (niad) that is upregulated upon induction of conidiation, even under n-repressing conditions in th ...201626353949
fungal cell cycle: a unicellular versus multicellular comparison.all cells must accurately replicate dna and partition it to daughter cells. the basic cell cycle machinery is highly conserved among eukaryotes. most of the mechanisms that control the cell cycle were worked out in fungal cells, taking advantage of their powerful genetics and rapid duplication times. here we describe the cell cycles of the unicellular budding yeast saccharomyces cerevisiae and the multicellular filamentous fungus aspergillus nidulans. we compare and contrast morphological landma ...201628087934
a class 1 histone deacetylase with potential as an antifungal target.histone deacetylases (hdacs) remove acetyl moieties from lysine residues at histone tails and nuclear regulatory proteins and thus significantly impact chromatin remodeling and transcriptional regulation in eukaryotes. in recent years, hdacs of filamentous fungi were found to be decisive regulators of genes involved in pathogenicity and the production of important fungal metabolites such as antibiotics and toxins. here we present proof that one of these enzymes, the class 1 type hdac rpda, is of ...201627803184
fungal sex: the ascomycota.this article provides an overview of sexual reproduction in the ascomycetes, a phylum of fungi that is named after the specialized sacs or "asci" that hold the sexual spores. they have therefore also been referred to as the sac fungi due to these characteristic structures that typically contain four to eight ascospores. ascomycetes are morphologically diverse and include single-celled yeasts, filamentous fungi, and more complex cup fungi. the sexual cycles of many species, including those of the ...201627763253
contribution of molecular tools for the diagnosis and epidemiology of fungal chronic rhinosinusitis.chronic rhinosinusitis (crs) rank second at chronic inflammatory diseases in industrialized countries and are an important public health concern. diagnosis relies on a set of arguments including clinical signs, imaging, histopathologic and mycological analyses of sinus specimens, collected during nasal endoscopy. the sensitivity of fungal cultures is reported to be poor, even when direct examination is positive, thus the epidemiology of fungal chronic sinusitis is ill-known. this study evaluated ...201627335058
decreased cell wall galactosaminogalactan in aspergillus nidulans mediates dysregulated inflammation in the chronic granulomatous disease host.invasive aspergillosis is a major threat to patients suffering from impaired neutrophil function, with aspergillus fumigatus being the most common species causing this life-threatening condition. patients with chronic granulomatous disease (cgd) not only develop infections with a. fumigatus, but also exhibit a unique susceptibility to infection with the normally nonpathogenic species aspergillus nidulans. in this study, we compared the inflammatory cytokine response of peripheral blood mononucle ...201627142572
new applications for known drugs: human glycogen synthase kinase 3 inhibitors as modulators of aspergillus fumigatus growth.invasive aspergillosis (ia) is one of the most severe forms of fungi infection. ia disease is mainly due to aspergillus fumigatus, an air-borne opportunistic pathogen. mortality rate caused by ia is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment options, thus new and efficient drugs are necessary. the aim of this work is, using aspergillus nidulans as non-pathogen model, to develop efficient drugs to treat ia. the recent discovered role of g ...201627131621
structural divergence of the group i intron binding surface in fungal mitochondrial tyrosyl-trna synthetases that function in rna splicing.the mitochondrial tyrosyl-trna synthetases (mttyrrss) of pezizomycotina fungi, a subphylum that includes many pathogenic species, are bifunctional proteins that both charge mitochondrial trna(tyr) and act as splicing cofactors for autocatalytic group i introns. previous studies showed that one of these proteins, neurospora crassa cyt-18, binds group i introns by using both its n-terminal catalytic and c-terminal anticodon binding domains and that the catalytic domain uses a newly evolved group i ...201627036943
subcellular compartmentalization and trafficking of the biosynthetic machinery for fungal melanin.protection by melanin depends on its subcellular location. although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. using a forward genetic screen in the pathogen aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. we find that all enzymes involved in the early steps of melanin biosynthesis are recru ...201626972005
distinct roles of myosins in aspergillus fumigatus hyphal growth and pathogenesis.myosins are a family of actin-based motor proteins found in many organisms and are categorized into classes based on their structures. class ii and v myosins are known to be important for critical cellular processes, including cytokinesis, endocytosis, exocytosis, and organelle trafficking, in the model fungi saccharomyces cerevisiae and aspergillus nidulans however, the roles of myosins in the growth and virulence of the pathogen aspergillus fumigatus are unknown. we constructed single- and dou ...201626953327
three extracellular dipeptidyl peptidases found in aspergillus oryzae show varying substrate specificities.three extracellular dipeptidyl peptidase genes, dppb, dppe, and dppf, were unveiled by sequence analysis of the aspergillus oryzae genome. we investigated their differential enzymatic profiles, in order to gain an understanding of the diversity of these genes. the three dipeptidyl peptidases were expressed using aspergillus nidulans as the host. each recombinant enzyme was purified and subsequently characterized. the enzymes displayed similar optimum ph values, but optimum temperatures, ph stabi ...201626846741
the signal peptide peptidase sppa is involved in sterol regulatory element-binding protein cleavage and hypoxia adaptation in aspergillus nidulans.using forward genetics, we revealed that the signal peptide peptidase (spp) sppa, an aspartyl protease involved in regulated intramembrane proteolysis (rip), is essential for hypoxia adaptation in aspergillus nidulans, as well as hypoxia-sensitive mutant alleles of a sterol regulatory element-binding protein (srebp) srba and the dsc ubiquitin e3 ligase complex dsca-e. both null and dead activity [d337a] mutants of sppa failed to grow in hypoxia, and the growth defect of δsppa was complemented by ...201626822492
identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis.during recent decades, the number of invasive fungal infections among immunosuppressed patients has increased significantly, whereas the number of effective systemic antifungal drugs remains low and unsatisfactory. the aim of this study was to characterize a novel antifungal compound, cw-8/haemofungin, which we previously identified in a screen for compounds affecting fungal cell wall integrity.201626747101
functional analysis of the nitrogen metabolite repression regulator gene nmra in aspergillus flavus.in aspergillus nidulans, the nitrogen metabolite repression (nmr) regulator nmra plays a major role in regulating the activity of the gata transcription factor area during nitrogen metabolism. however, the function of nmra in a. flavus has not been previously studied. here, we report the identification and functional analysis of nmra in a. flavus. our work showed that the amino acid sequences of nmra are highly conserved among aspergillus species and that a. flavus nmra protein contains a canoni ...201627933036
negative regulation and developmental competence in aspergillus.asexual development (conidiation) in the filamentous fungus aspergillus nidulans is governed by orchestrated gene expression. the three key negative regulators of conidiation sfga, vosa, and nsdd act at different control point in the developmental genetic cascade. here, we have revealed that nsdd is a key repressor affecting the quantity of asexual spores in aspergillus. moreover, nullifying both nsdd and vosa results in abundant formation of the development specific structure conidiophores even ...201627364479
rmta, a putative arginine methyltransferase, regulates secondary metabolism and development in aspergillus flavus.aspergillus flavus colonizes numerous oil seed crops such as corn, peanuts, treenuts and cotton worldwide, contaminating them with aflatoxin and other harmful potent toxins. in the phylogenetically related model fungus aspergillus nidulans, the methyltransferase, rmta, has been described to be involved in epigenetics regulation through histone modification. epigenetics regulation affects a variety of cellular processes, including morphogenesis and secondary metabolism. our study shows that delet ...201627213959
pharmacokinetic/pharmacodynamic analysis of voriconazole against candida spp. and aspergillus spp. in children, adolescents and adults by monte carlo simulation.the objective of this study was to investigate the cumulative fraction of response of various voriconazole dosing regimens against six candida and six aspergillus spp. in immunocompromised children, immunocompromised adolescents, and adults. using pharmacokinetic parameters and pharmacodynamic data, 5000-subject monte carlo simulations (mcss) were conducted to evaluate the ability of simulated dosing strategies in terms of fauc/mic targets of voriconazole. according to the results of the mcss, c ...201627179818
rtfa, a putative rna-pol ii transcription elongation factor gene, is necessary for normal morphological and chemical development in aspergillus flavus.the filamentous fungus aspergillus flavus is an agriculturally important opportunistic plant pathogen that produces potent carcinogenic compounds called aflatoxins. we identified the a. flavus rtfa gene, the ortholog of rtf1 in saccharomyces cerevisiae and rtfa in aspergillus nidulans. interestingly, rtfa has multiple cellular roles in this mycotoxin-producing fungus. in this study, we show that rtfa regulates conidiation. the rtfa deletion mutant presented smaller conidiophores with significant ...201627020290
occurrence of moulds from bee pollen in central italy--a preliminary study.the present study aimed to preliminary evaluate the occurrence of fungi in 40 specimens of trapped pollen collected from april-september 2015 in 40 apiaries from tuscany (central italy). cultural and microscopical examinations allowed the recognition of cladosporium sp., alternaria sp., humicola sp. mucoraceae and acremonium sp. penicillium brevicompactum, penicillium chrysogenum, aspergillus flavus , aspergillus nidulans, aspergillus niger and aspergillus terreus were also identified. yeasts an ...201627010410
the glycolytic enzyme enolase represents a plasminogen-binding protein on the surface of a wide variety of medically important fungal species.allergies are an increasing issue in human health and can, eventually, cause severe anaphylactic shock. aspergillus fumigatus and candida albicans are leading causes of life-threatening invasive fungal infections in immunocompromised patients, but can also cause severe allergic responses in otherwise healthy individuals. the glycolytic enzyme enolase is known as a major allergen despite its function in intracellular metabolism. therefore, its presentation on surfaces of different fungal species ...201626679571
linker flexibility facilitates module exchange in fungal hybrid pks-nrps engineering.polyketide synthases (pkss) and nonribosomal peptide synthetases (nrpss) each give rise to a vast array of complex bioactive molecules with further complexity added by the existence of natural pks-nrps fusions. rational genetic engineering for the production of natural product derivatives is desirable for the purpose of incorporating new functionalities into pre-existing molecules, or for optimization of known bioactivities. we sought to expand the range of natural product diversity by combining ...201627551732
proteolytic activation of both components of the cation stress-responsive slt pathway in aspergillus nidulans.tolerance of aspergillus nidulans to alkalinity and elevated cation concentrations requires both slta and sltb. transcription factor slta and the putative pseudokinase/protease signaling protein sltb comprise a regulatory pathway specific to filamentous fungi. in vivo, sltb is proteolytically cleaved into its two principal domains. mutational analysis defines a chymotrypsin-like serine protease domain that mediates sltb autoproteolysis and proteolytic cleavage of slta. the pseudokinase domain mi ...201627307585
biosynthetic pathway of the reduced polyketide product citreoviridin in aspergillus terreus var. aureus revealed by heterologous expression in aspergillus nidulans.citreoviridin (1) belongs to a class of f1-atpase β-subunit inhibitors that are synthesized by highly reducing polyketide synthases. these potent mycotoxins share an α-pyrone polyene structure, and they include aurovertin, verrucosidin, and asteltoxin. the identification of the citreoviridin biosynthetic gene cluster in aspergillus terreus var. aureus and its reconstitution using heterologous expression in aspergillus nidulans are reported. two intermediates were isolated that allowed the propos ...201626954888
the construction and use of versatile binary vectors carrying pyrg auxotrophic marker and fluorescent reporter genes for agrobacterium-mediated transformation of aspergillus oryzae.aspergillus oryzae is a safe mold widely used in food industry. it is also considered as a microbial cell factory for production of recombinant proteins and enzymes. currently, genetic manipulation of filamentous fungi is achieved via agrobacterium tumefaciens-mediated transformation methods usually employing antibiotic resistance markers. these methods are hardly usable for a. oryzae due to its strong resistance to the common antifungal compounds used for fungal transformation. in this study, w ...201627804102
generation of β-glucuronidase reporter-tagged strain to monitor ustilaginoidea virens infection in rice.an agrobacterium-mediated genetic transformation system for the rice false smut fungus ustilaginoidea virens was developed using conidia as recipients. a binary vector, pcambia1301-pgpda-gus-ttrpc, was constructed. the gpda promoter (pgpda) from aspergillus nidulans was used to drive the expression of the β-glucuronidase (gus) gene which enabled gus activity visualization. the conidia transformation efficiency reached approximately 110 to 250 transformants per 1×10(5) conidia. based on the analy ...201627789314
novel enzyme family found in filamentous fungi catalyzing trans-4-hydroxylation of l-pipecolic acid.hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. we have found a novel hydroxylating enzyme with activity toward l-pipecolic acid (l-pip) in a filamentous fungus, fusarium oxysporum c8d. the enzyme l-pip trans-4-hydroxylase (pip4h) of f. oxysporum (fopip4h) belongs to the fe(ii)/α-ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio- and stereoselective hydroxylation of l-pip ...201626801577
the selective expression of carbonic anhydrase genes of aspergillus nidulans in response to changes in mineral nutrition and co2 concentration.carbonic anhydrase (ca) plays an important role in the formation and evolution of life. however, to our knowledge, there has been no report on ca isoenzyme function differentiation in fungi. two different ca gene sequences in aspergillus nidulans with clear genetic background provide us a favorable basis for studying function differentiation of ca isoenzymes. heterologously expressed ca1 was used to test its weathering ability on silicate minerals and real-time quantitative pcr was used to detec ...201526553629
microbial communication leading to the activation of silent fungal secondary metabolite gene clusters.microorganisms form diverse multispecies communities in various ecosystems. the high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. a key role in this communication is played by secondary metabolites (sms), which are also called natural products. recently, it was shown that interspecies "talk" between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel sms ...201525941517
evaluation of aerial microbial pollutants in al-haram al-nabawi during pilgrimage of 2013.al-madinah al-munawwarah is the second holiest site in islam. the possibility of new emerging microbes is valid due to the increased number of pilgrims. the objectives of the current study were to estimate the numbers of fungi and bacteria inside and outside al-haram al-nabawi and to find whether new bacterial and fungal species have emerged compared to previous studies. air samples were collected twice a day from 12 spots and four directions during the pilgrim year of 2013 for four consecutive ...201528053593
agrobacterium tumefaciens-mediated transformation of the entomopathogenic fungus nomuraea rileyi.an agrobacterium-mediated genetic transformation system for the entomopathogenic fungus nomuraea rileyi was established. three binary t-dna vectors, ppzp-hph, ppzp-hph-rnai and ppzp-hph-dsred2, were constructed. the trpc promoter from aspergillus nidulans was used as the cis-regulatory element to drive the expression of hygromycin phosphotransferase (hph) gene and dsred2, which conferred the hygromycin b (hyg b) resistance and red fluorescence visualization, respectively. the blastospores and co ...201526275508
genetic transformation of extremophilic fungi acidea extrema and acidothrix acidophila.intact, growing cells of strongly acidophilic fungi acidea extrema and acidothrix acidophila have been successfully transformed by introduction of heterologous dna fragment (composed of the glyceraldehyde-phosphate-dehydrogenase gene promoter from emericella nidulans, a metallothionein-coding gene asmt1 from amanita strobiliformis and glyceraldehyde-phosphate-dehydrogenase gene terminator from colletotrichum gloeosporioides) with the length of 1690 bp. the transformation procedure was based on t ...201525934267
snpks19 encodes the polyketide synthase for alternariol mycotoxin biosynthesis in the wheat pathogen parastagonospora nodorum.alternariol (aoh) is an important mycotoxin from the alternaria fungi. aoh was detected for the first time in the wheat pathogen parastagonospora nodorum in a recent study. here, we exploited reverse genetics to demonstrate that snog_15829 (snpks19), a close homolog of penicillium aethiopicum norlichexanthone (nlx) synthase gene gsfa, is required for aoh production. we further validate that snpks19 is solely responsible for aoh production by heterologous expression in aspergillus nidulans. the e ...201526025896
pcr-rflp on β-tubulin gene for rapid identification of the most clinically important species of aspergillus.aspergillus species are important agents of life-threatening infections in immunosuppressed patients. proper speciation in the aspergilli has been justified based on varied fungal virulence, clinical presentations, and antifungal resistance. accurate identification of aspergillus species usually relies on fungal dna sequencing but this requires expensive equipment that is not available in most clinical laboratories. we developed and validated a discriminative low-cost pcr-based test to discrimin ...201526264625
hgt-finder: a new tool for horizontal gene transfer finding and application to aspergillus genomes.horizontal gene transfer (hgt) is a fast-track mechanism that allows genetically unrelated organisms to exchange genes for rapid environmental adaptation. we developed a new phyletic distribution-based software, hgt-finder, which implements a novel bioinformatics algorithm to calculate a horizontal transfer index and a probability value for each query gene. applying this new tool to the aspergillus fumigatus, aspergillus flavus, and aspergillus nidulans genomes, we found 273, 542, and 715 transf ...201526473921
the wopr domain protein osaa orchestrates development in aspergillus nidulans.orchestration of cellular growth and development occurs during the life cycle of aspergillus nidulans. a multi-copy genetic screen intended to unveil novel regulators of development identified the an6578 locus predicted to encode a protein with the wopr domain, which is a broadly present fungi-specific dna-binding motif. multi-copy of an6578 disrupted the normal life cycle of the fungus leading to enhanced proliferation of vegetative cells, whereas the deletion resulted in hyper-active sexual fr ...201526359867
development of the dichlorvos-ammonia (dv-am) method for the visual detection of aflatoxigenic fungi.aflatoxins (afs) are carcinogenic and toxic secondary metabolites produced mainly by aspergillus flavus and aspergillus parasiticus. to monitor and regulate the af contamination of crops, a sensitive and precise detection method for these toxigenic fungi in environments is necessary. we herein developed a novel visual detection method, the dichlorvos-ammonia (dv-am) method, for identifying af-producing fungi using dv and am vapor on agar culture plates, in which dv inhibits the esterase in af bi ...201526300294
association of fungal secondary metabolism and sclerotial biology.fungal secondary metabolism and morphological development have been shown to be intimately associated at the genetic level. much of the literature has focused on the co-regulation of secondary metabolite production (e.g., sterigmatocystin and aflatoxin in aspergillus nidulans and aspergillus flavus, respectively) with conidiation or formation of sexual fruiting bodies. however, many of these genetic links also control sclerotial production. sclerotia are resistant structures produced by a number ...201525762985
in vitro antioxidant and antidiabetic activities of biomodified lignin from acacia nilotica wood.the antioxidant and antidiabetic activity of biomodified alkali lignin extracted from a deciduous plant acacia nilotica, was evaluated in vitro. the extracted alkali lignin was subjected to microbial biotransformation by ligninolytic fungus aspergillus flavus and emericella nidulans. these modifications were done under varying concentration of carbon to nitrogen sources. the structural feature of the lignin samples were compared by ftir, functional group analysis and (13)c solid state nmr. all l ...201525600985
the fungal exopolysaccharide galactosaminogalactan mediates virulence by enhancing resistance to neutrophil extracellular traps.of the over 250 aspergillus species, aspergillus fumigatus accounts for up to 80% of invasive human infections. a. fumigatus produces galactosaminogalactan (gag), an exopolysaccharide composed of galactose and n-acetyl-galactosamine (galnac) that mediates adherence and is required for full virulence. less pathogenic aspergillus species were found to produce gag with a lower galnac content than a. fumigatus and expressed minimal amounts of cell wall-bound gag. increasing the galnac content of gag ...201526492565
fgric8 is involved in regulating vegetative growth, conidiation, deoxynivalenol production and virulence in fusarium graminearum.proteins of the resistance to inhibitors of cholinesterase 8 (ric8) group act as guanine nucleotide exchange factors (gefs) and play important roles in regulating g-protein signaling in animals. in filamentous fungi, putative ric8 orthologs have so far been identified in magnaporthe oryzae, neurospora crassa, aspergillus nidulans and aspergillus fumigatus. here, we report the functional investigation of a potential ric8 ortholog (fgric8) in the wheat head blight pathogen fusarium graminearum. ta ...201526341536
functional analysis of sterol transporter orthologues in the filamentous fungus aspergillus nidulans.polarized growth in filamentous fungi needs a continuous supply of proteins and lipids to the growing hyphal tip. one of the important membrane compounds in fungi is ergosterol. at the apical plasma membrane ergosterol accumulations, which are called sterol-rich plasma membrane domains (srds). the exact roles and formation mechanism of the srds remained unclear, although the importance has been recognized for hyphal growth. transport of ergosterol to hyphal tips is thought to be important for th ...201526116213
a pharmacokinetic/pharmacodynamic analysis of a standard voriconazole regimen in different cyp2c19 genotypes by monte carlo simulation.the objective of this study was to evaluate the standard voriconazole dosage regimen (maintenance dose was 200 mg bid orally) against aspergillus infections in different cyp2c19 genotypes from a pharmacokinetic/pharmacodynamic (pk/pd) perspective.201526062298
the aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.septins are a conserved family of gtpases that regulate important cellular processes such as cell wall integrity, and septation in fungi. the requirement of septins for virulence has been demonstrated in the human pathogenic yeasts candida albicans and cryptococcus neoformans, as well as the plant pathogen magnaporthe oryzae. aspergillus spp. contains five genes encoding for septins (aspa-e). while the importance of septins aspa, aspb, aspc, and aspe for growth and conidiation has been elucidate ...201526051489
the gβ-like protein cpcb is required for hyphal growth, conidiophore morphology and pathogenicity in aspergillus fumigatus.cpcb (cross pathway control b) encodes a yeast cpc2 and mammalian rack1 (receptor for activated protein kinase c) ortholog, which is a wd repeat protein with functional homology to the β subunit of heterotrimeric g proteins in aspergillus fumigatus. previous study has reported that cpcb governs growth and development in both a. fumigatus and aspergillus nidulans. however, little is known about the functional identities of cpcb orthologs and their relationships with g protein complexes. in this s ...201525892048
calcium signaling mediates antifungal activity of triazole drugs in the aspergilli.azoles are widely applied and largely effective as antifungals; however, the increasing prevalence of clinically resistant isolates has yet to be matched by approaches to improve the efficacy of antimicrobial therapy. in this study, using the model fungus aspergillus nidulans and one of the most common human pathogen aspergillus fumigatus as research materials, we present the evidence that calcium signaling is involved in the azole-antifungals-induced stress-response reactions. in normal media, ...201525554700
divergent targets of aspergillus fumigatus acuk and acum transcription factors during growth in vitro versus invasive disease.in aspergillus nidulans, the acuk and acum transcription factors form a complex that regulates gluconeogenesis. in aspergillus fumigatus, acum governs gluconeogenesis and iron acquisition in vitro and virulence in immunosuppressed mice. however, the function of acuk was previously unknown. through in vitro studies, we found that a. fumigatus δacuk single and δacuk δacum double mutants had impaired gluconeogenesis and iron acquisition, similar to the δacum mutant. also, the δacuk, δacum, and δacu ...201525534941
the apses family proteins in fungi: characterizations, evolution and functions.the apses protein family belongs to transcriptional factors of the basic helix-loop-helix (bhlh) class, the originally described members (apses: asm1p, phd1p, sok2p, efg1p and stuap) are used to designate this group of proteins, and they have been identified as key regulators of fungal development and other biological processes. apses proteins share a highly conserved dna-binding domain (apses domain) of about 100 amino acids, whose central domain is predicted to form a typical bhlh structure. b ...201525534868
redox metabolites signal polymicrobial biofilm development via the napa oxidative stress cascade in aspergillus.filamentous fungi and bacteria form mixed-species biofilms in nature and diverse clinical contexts. they secrete a wealth of redox-active small molecule secondary metabolites, which are traditionally viewed as toxins that inhibit growth of competing microbes.201525532893
soil fungi for mycoremediation of arsenic pollution in agriculture soils.soil arsenic (as) contamination of food-chains and public health can be mitigated through fungal bioremediation. to enumerate culturable soil fungi, soils were collected from the as-contaminated paddy fields (3-35 mg kg(-1) ) of the middle indo-gangetic plains.201526348882
identification of growth stage molecular markers in trichoderma sp. 'atroviride type b' and their potential application in monitoring fungal growth and development in soil.several members of the genus trichoderma are biocontrol agents of soil-borne fungal plant pathogens. the effectiveness of biocontrol agents depends heavily on how they perform in the complex field environment. therefore, the ability to monitor and track trichoderma within the environment is essential to understanding biocontrol efficacy. the objectives of this work were to: (a) identify key genes involved in trichoderma sp. 'atroviride type b' morphogenesis; (b) develop a robust rna isolation me ...201526341342
involvement of lipocalin-like cgha in decalin-forming stereoselective intramolecular [4+2] cycloaddition.understanding enzymatic diels-alder (da) reactions that can form complex natural product scaffolds is of considerable interest. sch 210972 1, a potential anti-hiv fungal natural product, contains a decalin core that is proposed to form through a da reaction. we identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in aspergillus nidulans to characterize the enzymes involved. most notably, deletion of cgha resulted in a loss of ...201526360642
dissecting the function of the different chitin synthases in vegetative growth and sexual development in neurospora crassa.chitin, one of the most important carbohydrates of the fungal cell wall, is synthesized by chitin synthases (chs). seven sequences encoding chss have been identified in the genome of neurospora crassa. previously, chs-1, -3 and -6 were found at the spitzenkörper(spk) core and developing septa. we investigated the functional importance of each chs in growth and development of n. crassa. the cellular distribution of each chs tagged with fluorescent proteins and the impact of corresponding gene del ...201525596036
erratum to: a novel thermophilic endo-β-1,4-mannanase from aspergillus nidulans xz3: functional roles of carbohydrate-binding module and thr/ser-rich linker region. 201525520174
γ-glutamyl transpeptidase (ggta) of aspergillus nidulans is not necessary for bulk degradation of glutathione.aspergillus nidulans exhibited high γ-glutamyl transpeptidase (γgt) activity in both carbon-starved and carbon-limited cultures. glucose repressed, but casein peptone increased γgt production. null mutation of crea did not influence γgt formation, but the functional meab was necessary for the γgt induction. deletion of the an10444 gene (ggta) completely eliminated the γgt activity, and the mrna levels of ggta showed strong correlation with the observed γgt activities. while ggta does not contain ...201525519188
identification and structural elucidation of ergotryptamine, a new ergot alkaloid produced by genetically modified aspergillus nidulans and natural isolates of epichloë species.ergot alkaloid pathway reconstruction in aspergillus nidulans is an approach used to better understand the biosynthesis of these mycotoxins. an engineered strain named a. nidulans wfc (expressing ergot alkaloid synthesis genes dmaw, easf, and easc) produced the established intermediate n-methyl-4-dimethylallyltryptophan, as well as an uncharacterized ergot alkaloid. we investigated the chemical structure of the new metabolite and its role in the ergot alkaloid pathway. mass spectrometry, labelin ...201525491167
the old 3-oxoadipate pathway revisited: new insights in the catabolism of aromatics in the saprophytic fungus aspergillus nidulans.aspergilli play major roles in the natural turnover of elements, especially through the decomposition of plant litter, but the end catabolism of lignin aromatic hydrocarbons remains largely unresolved. the 3-oxoadipate pathway of their degradation combines the catechol and the protocatechuate branches, each using a set of specific genes. however, annotation for most of these genes is lacking or attributed to poorly- or un-characterised families. aspergillus nidulans can utilise as sole carbon/en ...201525479309
conditional inactivation of aspergillus nidulans sara(sar1) uncovers the morphogenetic potential of regulating endoplasmic reticulum (er) exit.in the genetic model aspergillus nidulans, hyphal growth is exquisitely dependent on exocytic traffic. following mutagenic pcr and gene replacement, we characterized thermosensitive mutations in sara(sar1) encoding a key regulator of endoplasmic reticulum (er) exit. six sara(ts) alleles permitting relatively normal growth at 30°c prevented it at 42°c. this growth phenotype correlated with markedly reduced sara levels at high temperature, suggesting that these alleles cause temperature-dependent ...201525425159
spatial regulation of the spindle assembly checkpoint and anaphase-promoting complex in aspergillus nidulans.the spindle assembly checkpoint (sac) plays a critical role in preventing mitotic errors by inhibiting anaphase until all kinetochores are correctly attached to spindle microtubules. in spite of the economic and medical importance of filamentous fungi, relatively little is known about the behavior of sac proteins in these organisms. in our efforts to understand the role of γ-tubulin in cell cycle regulation, we have created functional fluorescent protein fusions of four sac proteins in aspergill ...201525417844
rite of passage: a bzip transcription factor must transit the cell apex to become competent.in the filamentous fungus aspergillus nidulans brla triggers the central developmental pathway that controls the transition from vegetative growth to asexual reproduction. upstream regulators including the bzip transcription factor flbb activate the expression of brla. previous work has established that flbb localizes to both the apex of the hypha, where it interacts with and is anchored by flbe, and to nuclei, with highest levels in the nucleus closest to the apex and successively lower levels ...201526387769
novel β-1,4-mannanase belonging to a new glycoside hydrolase family in aspergillus nidulans.many filamentous fungi produce β-mannan-degrading β-1,4-mannanases that belong to the glycoside hydrolase 5 (gh5) and gh26 families. here we identified a novel β-1,4-mannanase (man134a) that belongs to a new glycoside hydrolase (gh) family (gh134) in aspergillus nidulans. blast analysis of the amino acid sequence using the ncbi protein database revealed that this enzyme had no similarity to any sequences and no putative conserved domains. protein homologs of the enzyme were distributed to limite ...201526385921
discovery of a vezatin-like protein for dynein-mediated early endosome transport.early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. here our forward genetic study led to the discovery of veza, a vezatin-like protein in aspergillus nidulans, as a factor critical for early endosome distribution. loss of veza causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. this abnormal accumulation depends on kinesin-3 and is due to a dec ...201526378255
extreme diversity in the regulation of ndt80-like transcription factors in fungi.the saccharomyces cerevisiae ndt80 protein is the founding member of a class of p53-like transcription factors that is known as the ndt80/phog-like dna-binding family. the number of ndt80-like genes in different fungi is highly variable and their roles, which have been examined in only a few species, include regulation of meiosis, sexual development, biofilm formation, drug resistance, virulence, the response to nutrient stress and programmed cell death. the protein kinase ime2 regulates the sin ...201526497142
characterization of annce102 and its role in eisosome stability and sphingolipid biosynthesis.the plasma membrane is implicated in a variety of functions, whose coordination necessitates highly dynamic organization of its constituents into domains of distinct protein and lipid composition. eisosomes, at least partially, mediate this lateral plasma membrane compartmentalization. in this work, we show that the nce102 homologue of aspergillus nidulans colocalizes with eisosomes and plays a crucial role in density/number of pila/surg foci in the head of germlings. in addition we demonstrate ...201526468899
deciphering the combinatorial dna-binding code of the ccaat-binding complex and the iron-regulatory basic region leucine zipper (bzip) transcription factor hapx.the heterotrimeric ccaat-binding complex (cbc) is evolutionarily conserved in eukaryotic organisms, including fungi, plants, and mammals. the cbc consists of three subunits, which are named in the filamentous fungus aspergillus nidulans hapb, hapc, and hape. hapx, a fourth cbc subunit, was identified exclusively in fungi, except for saccharomyces cerevisiae and the closely related saccharomycotina species. the cbc-hapx complex acts as the master regulator of iron homeostasis. hapx belongs to the ...201525589790
the aspergillus nidulans proline permease as a model for understanding the factors determining substrate binding and specificity of fungal amino acid transporters.amino acid uptake in fungi is mediated by general and specialized members of the yeast amino acid transporter (yat) family, a branch of the amino acid polyamine organocation (apc) transporter superfamily. prnb, a highly specific l-proline transporter, only weakly recognizes other put4p substrates, its saccharomyces cerevisiae orthologue. taking advantage of the high sequence similarity between the two transporters, we combined molecular modeling, induced fit docking, genetic, and biochemical app ...201525572393
riboflavin level manipulates the successive developmental sequences in aspergillus nidulans.auxotrophic markers are useful in fungal genetic analysis. among the auxotrophic markers, ribob2 is one of the most commonly used markers in many laboratory strains. however, ribob2 mutants in aspergillus nidulans confer self-sterility and thus are unable to form hybrid cleistothecia by outcross when both parent strains harbor ribob2 auxotrophic marker under the standard protocol. to assess the role of riboflavin during the different developmental stages of a. nidulans, the limited concentration ...201525567479
increased production of free fatty acids in aspergillus oryzae by disruption of a predicted acyl-coa synthetase gene.fatty acids are attractive molecules as source materials for the production of biodiesel fuel. previously, we attained a 2.4-fold increase in fatty acid production by increasing the expression of fatty acid synthesis-related genes in aspergillus oryzae. in this study, we achieved an additional increase in the production of fatty acids by disrupting a predicted acyl-coa synthetase gene in a. oryzae. the a. oryzae genome is predicted to encode six acyl-coa synthetase genes and disruption of ao0900 ...201525564035
characterization of npga, a 4'-phosphopantetheinyl transferase of aspergillus nidulans, and evidence of its involvement in fungal growth and formation of conidia and cleistothecia for development.the null pigmentation mutant (npga1) in aspergillus nidulans results in a phenotype with colorless organs, decreased branching growth, delayed of asexual spore development, and aberrant cell wall structure. the npga gene was isolated from a. nidulans to investigate these pleiomorphic phenomena of npga1 mutant. sequencing analysis of the complementing gene indicated that it contained a 4'-phosphopantetheinyl transferase (pptase) superfamily domain. enzymatic assay of the pptase, encoded by the np ...201525557478
neurospora crassa asm-1 complements the conidiation defect in a stua mutant of aspergillus nidulans.aspergillus nidulans stua and neurospora crassa asm-1 are orthologous apses (asm-1, phd1, sok2, efg1, stua) transcription factors conserved across a diverse group of fungi. stua and asm-1 have roles in asexual (conidiation) and sexual (ascospore formation) development in both organisms. to address the hypothesis that the last common ancestor of these diverse fungi regulated conidiation with similar genes, asm-1 was introduced into the stua1 mutant of a. nidulans. expression of asm-1 complemented ...201525550299
preparative separation of echinocandin b from aspergillus nidulans broth using macroporous resin adsorption chromatography.echinocandin b (ecb), an echinocandin type of lipopeptide antibiotic produced by aspergillus nidulans, is a precursor for the synthesis of novel anti-fungal drug - anidulafungin. in this work, a separation strategy involving one-step macroporous resin adsorption chromatography was established for ecb purification from aspergillus nidulans cctcc m 2010275 fermentation broth. among nine macroporous resin adsorbents tested, the non-polar resin hp-20 had the best adsorption and desorption performanc ...201525541471
nup2 requires a highly divergent partner, nupa, to fulfill functions at nuclear pore complexes and the mitotic chromatin region.chromatin and nuclear pore complexes (npcs) undergo dramatic changes during mitosis, which in vertebrates and aspergillus nidulans involves movement of nup2 from npcs to the chromatin region to fulfill unknown functions. this transition is shown to require the cdk1 mitotic kinase and be promoted prematurely by ectopic expression of the nima kinase. nup2 localizes with a copurifying partner termed nupa, a highly divergent yet essential npc protein. nupa and nup2 locate throughout the chromatin re ...201525540430
pdbrla, pdabaa and pdweta control distinct stages of conidiogenesis in penicillium digitatum.penicillium digitatum is one of the most important citrus postharvest pathogens worldwide. reproduction of massive asexual spores is the primary factor contributing to the epidemic of citrus green mold. to understand the molecular mechanisms underlying conidiogenesis in p. digitatum, we functionally characterized the aspergillus nidulans orthologs of brla, abaa and weta. we showed that deletion of pdbrla completely blocked formation of conidiophores, whereas deletion of pdabaa led to the formati ...201525530311
fusarium sambucinum asta gene expressed during potato infection is a functional orthologue of aspergillus nidulans asta.sulfate assimilation plays a vital role in prototrophic organisms. orthologues of the alternative sulfate transporter (asta) gene from aspergillus nidulans were identified in the fungal plant pathogens fusarium sambucinum and fusarium graminearum. by physiological and biochemical analyses, the asta orthologues were determined to be able to uptake sulfate from the environment. similarly to asta in a. nidulans, the fsasta gene was found to be regulated by sulfur metabolite repression (smr) in a su ...201525986548
brain abscesses due to aspergillus nidulans infection during induction chemotherapy for acute lymphoblastic leukemia.we present the case of a 3-year-old boy who was diagnosed with cerebral abscesses due to aspergillus nidulans infection on day 28 of induction chemotherapy for acute lymphoblastic leukemia. he responded well to treatment with voriconazole and caspofungin, making a full recovery. there are very few cases of invasive aspergillosis reported in children during induction chemotherapy for acute leukemia and a. nidulans is rare in the absence of chronic granulomatous disease.201525985238
successful combination of sequential gene therapy and rescue allo-hsct in two children with x-cgd - importance of timing.we report on a series of sequential events leading to long-term survival and cure of pediatric x-linked chronic granulomatous disease (x-cgd) patients after gamma-retroviral gene therapy (gt) and rescue hsct. due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (hsct) but absence of hlaidentical donors, we treated 2 boys with x-cgd by gt. following gt both children completely resolved invasive aspergillus nidulans infections. however, one child d ...201525981636
light-dependent gene activation in aspergillus nidulans is strictly dependent on phytochrome and involves the interplay of phytochrome and white collar-regulated histone h3 acetylation.the ability for light sensing is found from bacteria to humans but relies only on a small number of evolutionarily conserved photoreceptors. a large number of fungi react to light, mostly to blue light. aspergillus nidulans also responds to red light using a phytochrome light sensor, fpha, for the control of hundreds of light-regulated genes. here, we show that photoinduction of one light-induced gene, ccga, occurs mainly through red light. induction strictly depends on phytochrome and its histi ...201525980340
velvet-mediated repression of β-glucan synthesis in aspergillus nidulans spores.beta-glucans are a heterologous group of fibrous glucose polymers that are a major constituent of cell walls in ascomycetes and basidiomycetes fungi. synthesis of β (1,3)- and (1,6)-glucans is coordinated with fungal cell growth and development, thus, is under tight genetic regulation. here, we report that β-glucan synthesis in both asexual and sexual spores is turned off by the nf-kb like fungal regulators vosa and velb in aspergillus nidulans. our genetic and genomic analyses have revealed tha ...201525960370
transportation of aspergillus nidulans class iii and v chitin synthases to the hyphal tips depends on conventional kinesin.cell wall formation and maintenance are crucial for hyphal morphogenesis. in many filamentous fungi, chitin is one of the main structural components of the cell wall. aspergillus nidulans chsb, a chitin synthase, and csma, a chitin synthase with a myosin motor-like domain (mmd) at its n-terminus, both localize predominantly at the hyphal tip regions and at forming septa. chsb and csma play crucial roles in polarized hyphal growth in a. nidulans. in this study, we investigated the mechanism by wh ...201525955346
the effects of extracellular ph and of the transcriptional regulator paci on the transcriptome of trichoderma reesei.extracellular ph is one of the several environmental factors affecting protein production by filamentous fungi. regulatory mechanisms ensure that extracellular enzymes are produced under ph-conditions in which the enzymes are active. in filamentous fungi, the transcriptional regulation in different ambient ph has been studied especially in aspergilli, whereas the effects of ph in the industrial producer of hydrolytic enzymes, trichoderma reesei, have mainly been studied at the protein level. in ...201525925231
a lipid-managing program maintains a stout spitzenkörper.the spitzenkörper (spk) is an accumulation of vesicles interleaved with actin microfilaments present at the cytosolic side of the apical plasma membrane (pm) of hyphal tips of many species of filamentous fungi. the physiological role of the spk has captivated fungal biologists over the years, but only very recently this 'organelle' is starting to be understood in the molecular terminology used for cell biological models. one aspect that has received little attention is the role of cellular membr ...201525921726
depletion of ε-cop in the copi vesicular coat reduces cleistothecium production in aspergillus nidulans.we have previously isolated ε-cop, the α-cop interactor in copi of aspergillus nidulans, by yeast two-hybrid screening. to understand the function of ε-cop, the anea (+) gene for ε-cop/anea was deleted by homologous recombination using a gene-specific disruption cassette. deletion of the ε-cop gene showed no detectable changes in vegetative growth or asexual development, but resulted in decrease in the production of the fruiting body, cleistothecium, under conditions favorable for sexual develop ...201525892912
regulation of glycogen metabolism by the cre-1, rco-1 and rcm-1 proteins in neurospora crassa. the role of cre-1 as the central transcriptional regulator.the transcription factor crea/mig1/cre-1 is a repressor protein that regulates the use of alternative carbon sources via a mechanism known as carbon catabolite repression (ccr). in saccharomyces cerevisiae, mig1 recruits the complex ssn6-tup1, the neurospora crassa rcm-1 and rco-1 orthologous proteins, respectively, to bind to promoters of glucose-repressible genes. we have been studying the regulation of glycogen metabolism in n. crassa and the identification of the rco-1 corepressor as a regul ...201525889113
cytoplasmic dynein is required for the spatial organization of protein aggregates in filamentous fungi.eukaryotes have evolved multiple strategies for maintaining cellular protein homeostasis. one such mechanism involves neutralization of deleterious protein aggregates via their defined spatial segregation. here, using the molecular disaggregase hsp104 as a marker for protein aggregation, we describe the spatial and temporal dynamics of protein aggregates in the filamentous fungus aspergillus nidulans. filamentous fungi, such as a. nidulans, are a diverse group of species of major health and econ ...201525865884
the cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator.the rim101/pacc transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular ph signals. first characterized in ascomycete fungi such as aspergillus nidulans and saccharomyces cerevisiae, the rim/pal pathway maintains conserved features among very distantly related fungi, where it coordinates cellular adaptation to alkaline ph signals and micronutrient deprivation. however, it also directs species-specific functions in fungal pathogens such as cryptococc ...201525859664
structural and functional analysis of the rpf2-rrs1 complex in ribosome biogenesis.proteins rpf2 and rrs1 are required for 60s ribosomal subunit maturation. these proteins are necessary for the recruitment of three ribosomal components (5s ribosomal rna [rrna], rpl5 and rpl11) to the 90s ribosome precursor and subsequent 27sb pre-rrna processing. here we present the crystal structure of the aspergillus nidulans (an) rpf2-rrs1 core complex. the core complex contains the tightly interlocked n-terminal domains of rpf2 and rrs1. the rpf2 n-terminal domain includes a brix domain ch ...201525855814
high-affinity nitrate/nitrite transporters nrta and nrtb of aspergillus nidulans exhibit high specificity and different inhibitor sensitivity.the nrta and nrtb nitrate transporters are paralogous members of the major facilitator superfamily in aspergillus nidulans. the availability of loss-of-function mutations allowed individual investigation of the specificity and inhibitor sensitivity of both nrta and nrtb. in this study, growth response tests were carried out at a growth-limiting concentration of nitrate (1 mm) as the sole nitrogen source, in the presence of a number of potential nitrate analogues at various concentrations, to eva ...201525855763
a new high-performance heterologous fungal expression system based on regulatory elements from the aspergillus terreus terrein gene cluster.recently, the aspergillus terreus terrein gene cluster was identified and selected for development of a new heterologous expression system. the cluster encodes the specific transcription factor terr that is indispensable for terrein cluster induction. to identify terr binding sites, different recombinant versions of the terr dna-binding domain were analyzed for specific motif recognition. the high affinity consensus motif tcgghhwyhcggh was identified from genes required for terrein production an ...201525852654
the bzip transcription factor pfzipa regulates secondary metabolism and oxidative stress response in the plant endophytic fungus pestalotiopsis fici.the bzip transcription factors are conserved in all eukaryotes and play critical roles in organismal responses to environmental challenges. in filamentous fungi, several lines of evidence indicate that secondary metabolism (sm) is associated with oxidative stress mediated by bzip proteins. here we uncover a connection with a bzip protein and oxidative stress induction of sm in the plant endophytic fungus pestalotiopsis fici. a homology search of the p. fici genome with the bzip protein rsma, inv ...201525847004
aspergillus nidulans flippase dnfa is cargo of the endocytic collar and plays complementary roles in growth and phosphatidylserine asymmetry with another flippase, dnfb.endocytosis and exocytosis are strictly segregated at the ends of hyphal cells of filamentous fungi, with a collar of endocytic activity encircling the growing cell tip, which elongates through directed membrane fusion. it has been proposed that this separation supports an endocytic recycling pathway that maintains polar localization of proteins at the growing apex. in a search for proteins in the filamentous fungus aspergillus nidulans that possess an npfxd motif, which signals for endocytosis, ...201525846564
integration of the catalytic subunit activates deneddylase activity in vivo as final step in fungal cop9 signalosome assembly.the eight-subunit cop9 signalosome (csn) is conserved from filamentous fungi to humans and functions at the interface between cellular signalling and protein half-life control. csn consists of six pci and two mpn domain proteins and forms a scaffold for additional interacting proteins. csn controls protein stability in the ubiquitin-proteasome system where the mpn domain csn5/csne subunit inactivates cullin-ring ligases. the csn5/csne isopeptidase functions as deneddylase and removes the ubiquit ...201525846252
aspergillus nidulans ambient ph signaling does not require endocytosis.aspergillus nidulans (pal) ambient ph signaling takes place in cortical structures containing components of the escrt pathway, which are hijacked by the alkaline ph-activated, ubiquitin-modified version of the arrestin-like protein palf and taken to the plasma membrane. there, escrts scaffold the assembly of dedicated pal proteins acting downstream. the molecular details of this pathway, which results in the two-step proteolytic processing of the transcription factor pacc, have received consider ...201525841020
trappii regulates exocytic golgi exit by mediating nucleotide exchange on the ypt31 ortholog raberab11.the oligomeric complex transport protein particle i (trappi) mediates nucleotide exchange on the rab gtpase rab1/ypt1. trappii is composed of trappi plus three additional subunits, trs120, trs130, and trs65. unclear is whether trappii mediates nucleotide exchange on rab1/ypt1, rab11/ypt31, or both. in aspergillus nidulans, rabo(rab1) resides in the golgi, rabe(rab11) localizes to exocytic post-golgi carriers undergoing transport to the apex, and hypa encodes trs120. rabe(rab11), but not rabo(rab ...201525831508
sphingolipids mediate differential echinocandin susceptibility in candida albicans and aspergillus nidulans.the cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. previous studies revealed that, in the haploid yeast candida glabrata, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (crs) but micafungin increased susceptibility (mis). here, we describe one candida albicans strain (of 10 tested) that similarly yields crs-mis mutants at relatively high frequency. m ...201525824222
azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.the aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including alzheimer's disease. the inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. we have previously screened aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in v ...201525822288
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