Polarized growth is a defining property of filamentous fungi, which plays an important role in different aspects of their biology, including virulence. However, little information is available about ...the determinants of cell surface organization and their role in polarized growth. The fungal protein MesA was identified in a genetic screen in Aspergillus nidulans and is involved in the stabilization of the polarity axes, but it has no evident role in budding yeast. In this work, I present evidence that in the dimorphic fungal phytopathogen Ustilago maydis MesA/Mes1 is involved in cell wall stability and polarized growth. mes1 mutants were more sensitive to drugs provoking cell wall stress, and they displayed a temperature-sensitive phenotype. Actin cytoskeleton was disorganized in a mes1 mutant, suggesting that there is a connection between Mes1, the actin cytoskeleton and polarized morphogenesis. The septin ring was also absent from the bud tip, but not the bud neck. Deletion of mes1 provoked defects in endocytosis and vacuolar organization in the cells. Mes1 was essential for strong polarized growth in the hyphal form, but it was dispensable during low or moderate polarized growth in the yeast form in U. maydis at a permissive temperature. Consistently, mes1 mutants showed delayed mating and they were avirulent.
The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent ...carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.
We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli.
Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
Summary Introduction Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in ...patients with acute ischaemic stroke. Methods URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received alteplase within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2). Patients were randomly allocated (1:1) to receive uric acid 1000 mg or placebo (both infused intravenously in 90 min during the infusion of alteplase), stratified by centre and baseline stroke severity. The primary outcome was the proportion of patients with excellent outcome (ie, an mRS score of 0–1, or 2 if premorbid score was 2) at 90 days, analysed in the target population (all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication). The study is registered with ClinicalTrials.gov , number NCT00860366. Findings Between July 1, 2011, and April 30, 2013, we randomly assigned 421 patients, of whom 411 (98%) were included in the target population (211 received uric acid and 200 received placebo). 83 (39%) patients who received uric acid and 66 (33%) patients who received placebo had an excellent outcome (adjusted risk ratio 1·23 95% CI 0·96–1·56; p=0·099). No clinically relevant or statistically significant differences were reported between groups with respect to death (28 13% patients who received uric acid vs 31 16% who received placebo), symptomatic intracerebral haemorrhage (nine 4% vs six 3%), and gouty arthritis (one <1% vs four 2%). 516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 (12%) and 67 (13%), respectively, were serious adverse events (p=0·703). Interpretation The addition of uric acid to thrombolytic therapy did not increase the proportion of patients who achieved excellent outcome after stroke compared with placebo, but it did not lead to any safety concerns. Funding Institute of Health Carlos III of the Spanish Ministry of Health and Fundación Doctor Melchor Colet.
Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental ...cues, including light, but the mechanisms are largely unknown 1. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis 2. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi 3–6. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.
•We sequenced the genomes of fungi Mucor circinelloides and Phycomyces blakesleeanus•Extensive genomic duplications increased the number of genes for signal transduction•After duplication, genes specialized their transcriptional regulation by light•Genome duplications provided new components to improve sensory perception in fungi
Fungi use light and other signals to regulate development, but the mechanisms and origin are largely unknown. Corrochano et al. have found that a group of fungi has acquired new components for signal transduction pathways after extensive genomic duplication. The expanded gene repertoire allows an enhanced perception of environmental signals.
OBJECTIVEWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by ...evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.
METHODSPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.
RESULTSWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval CI 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).
CONCLUSIONPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.
CLINICALTRIALS.GOV IDENTIFIERNCT02238470.
Nitric oxide (NO) is a remarkable gaseous molecule with multiple and important roles in different organisms, including fungi. However, the study of the biology of NO in fungi has been hindered by the ...lack of a complete knowledge on the different metabolic routes that allow a proper NO balance, and the regulation of these routes. Fungi have developed NO detoxification mechanisms to combat nitrosative stress, which have been mainly characterized by their connection to pathogenesis or nitrogen metabolism. However, the progress on the studies of NO anabolic routes in fungi has been hampered by efforts to disrupt candidate genes that gave no conclusive data until recently. This review summarizes the different roles of NO in fungal biology and pathogenesis, with an emphasis on the alternatives to explain fungal NO production and the recent findings on the involvement of nitrate reductase in the synthesis of NO and its regulation during fungal development.
Filamentous fungi naturally grow on solid surfaces, yet most genetic and biochemical analyses are still performed in liquid cultures. Here, we report a multiplexing platform using high-throughput ...photometric continuous reading that allows parallel quantification of hyphal growth and reporter gene expression directly on solid medium, thereby mimicking natural environmental conditions. Using this system, we have quantified fungal growth and expression of secondary metabolite GFP-based reporter genes in saprophytic Aspergillus and phytopathogenic Fusarium species in response to different nutrients, stress conditions and epigenetic modifiers. With this method, we provide not only novel insights into the characteristic of fungal growth but also into the metabolic and time-dependent regulation of secondary metabolite gene expression.
Microorganisms have evolved dynamic mechanisms for facing the toxicity of arsenic in the environment. In this sense, arsenic speciation and mobility is also affected by the microbial metabolism that ...participates in the biogeochemical cycle of the element. The ars operon constitutes the most ubiquitous and important scheme of arsenic tolerance in bacteria. This system mediates the extrusion of arsenite out of the cells. There are also other microbial activities that alter the chemical characteristics of arsenic: some strains are able to oxidize arsenite or reduce arsenate as part of their respiratory processes. These type of microorganisms require membrane associated proteins that transfer electrons from or to arsenic (AoxAB and ArrAB, respectively). Other enzymatic transformations, such as methylation-demethylation reactions, exchange inorganic arsenic into organic forms contributing to its complex environmental turnover. This short review highlights recent studies in ecology, biochemistry and molecular biology of these processes in bacteria, and also provides some examples of genetic engineering for enhanced arsenic accumulation based on phytochelatins or metallothionein-like proteins.
Fungi use light as an environmental signal to regulate developmental transitions that are key aspects of their biological cycles and that are also relevant for their dispersal and infectivity as ...plant or animal pathogens. In addition, light regulates the accumulation of photoprotective pigments, like carotenoids, and other secondary metabolites. Most fungal light responses occur after changes in gene transcription and we describe here a novel effect of light in the regulation of degradation of VE-1, a key component of the velvet complex, in the model fungus Neurospora crassa. The velvet complex is a fungal-specific protein complex that coordinates fungal development, secondary metabolism, and light regulation by interacting with other regulators and photoreceptors and modifying gene expression.
We have characterized the role of VE-1 during conidiation in N. crassa. In vegetative mycelia, VE-1 is localized in the cytoplasm and nuclei and is required for light-dependent transcription but does not interact with the photoreceptor and transcription factor WC-1. VE-1 is more stable in light than in darkness during asexual development (conidiation). We have shown that this light effect requires the blue-light photoreceptor WC-1. We have characterized the role of the proteasome, the COP9 signalosome (CSN), and the adaptor component of cullin-RING ubiquitin ligases, FWD-1, in the degradation of VE-1.
We propose that this new effect of light allows the fungal cell to adapt quickly to changes in light exposure by promoting the accumulation of VE-1 for the regulation of genes that participate in the biosynthesis of photoprotective pigments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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