A significant challenge in our understanding of biological systems is the high number of genes with unknown function in many genomes. The fungal genus Aspergillus contains important pathogens of humans, model organisms, and microbial cell factories. Aspergillus niger is used to produce organic acids, proteins, and is a promising source of new bioactive secondary metabolites. Out of the 14,165 open reading frames predicted in the A. niger genome only 2% have been experimentally verified and over 6,000 are hypothetical. Here, we show that gene co-expression network analysis can be used to overcome this limitation. A meta-analysis of 155 transcriptomics experiments generated co-expression networks for 9,579 genes (∼65%) of the A. niger genome. By populating this dataset with over 1,200 gene functional experiments from the genus Aspergillus and performing gene ontology enrichment, we could infer biological processes for 9,263 of A. niger genes, including 2,970 hypothetical genes. Experimental validation of selected co-expression sub-networks uncovered four transcription factors involved in secondary metabolite synthesis, which were used to activate production of multiple natural products. This study constitutes a significant step towards systems-level understanding of A. niger, and the datasets can be used to fuel discoveries of model systems, fungal pathogens, and biotechnology.
Our data suggest a fundamental role of glycosylceramides in the susceptibility of fungi to AFP. We discovered that only a minor structural difference in these molecules—namely, the saturation level of their fatty acid chain, controlled by a 2-hydroxy fatty N-acyl-Δ3(E)-desaturase—represents a key to understanding the inhibitory activity of AFP. As glycosylceramides are important components of fungal plasma membranes, we propose a model which links AFP-mediated inhibition of chitin synthesis in fungi with its potential to disturb plasma membrane integrity.
The particular questions asked in our study were: 1. does the individual reproducibility of the cardiovascular reflex tests differ between healthy controls and patients suffering from type I diabetes mellitus and 2. if there is a difference, do the different cardiovascular reflexes vary in this regard? Nine healthy controls (4 women, 5 men, age 31 +/- 2.1 years) and 11 type I diabetics (4 women, 7 men, age 30.9 +/- 5.6 years, duration of diabetes 3.23 years) underwent the following tests 6 times in a 12-h period (07:00 to 19:00): variation of heart rate during deep breathing (E/I ratio), variation of heart rate during lying and standing (tachycardia/bradycardia or 30/15 ratio), Valsalva maneuver (Valsalva ratio), response of diastolic blood pressure to sustained hand grip, and response of systolic blood pressure to posture. The test results did not indicate a diurnal fluctuation nor were they systematically influenced by antecedent insulin injections or meals, either in diabetic patients or in healthy controls. The 11 diabetics had significantly lower intraindividual variations of E/I and Valsalva ratios than the controls (p less than 0.05, p less than 0.001, respectively). In the diabetics with parasympathetic failure the intraindividual variabilities of all cardiovascular reflex responses were lower than those of the patients with an intact autonomic nervous system as well as those of the control subjects. On the contrary, in the diabetic patients without autonomic neuropathy, only the intraindividual variability of the Valsalva maneuver was significantly attenuated (p less than 0.025), compared with the healthy volunteers. To conclude, the more pathological the single test result, the greater is its reproducibility and its clinical significance.
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