Resynthesis of Damaged Fe-S Cluster Proteins Protects Against Oxidative Stress in the Absence of Mn-Superoxide Dismutase.

The importance of manganese superoxide dismutase (Mn-SOD), an evolutionarily ancient metalloenzyme that maintains the integrity and function of mitochondria, was studied in oxidative stress-treated cultures. Deletion of the Mn-SOD gene () increased both the menadione sodium bisulfite (MSB)-elicited oxidative stress and the deferiprone (DFP)-induced iron limitation stress sensitivity of the strain. Moreover, DFP treatment enhanced the MSB sensitivity of both the gene deletion mutant and the reference strain.

, Encoding the Hyperosmotic Stress Protein Glycerol-3-phosphate Dehydrogenase, Disrupts Osmoadaptation in .

The genome of the osmophilic , unlike that of the osmotolerant , contains only the , but not the , glycerol 3-phosphate dehydrogenase gene. Here, we studied transcriptomic changes of (reference strain and Δ gene deletion mutant) and (reference strain and expressing mutant) elicited by high osmolarity. showed a canonic hyperosmotic stress response characterized by the upregulation of the trehalose and glycerol metabolism genes (including ), as well as the genes of the high-osmolarity glycerol (HOG) map kinase pathway.

Total transcriptome response for tyrosol exposure in Aspergillus nidulans.

Although tyrosol is a quorum-sensing molecule of Candida species, it has antifungal activity at supraphysiological concentrations. Here, we studied the effect of tyrosol on the physiology and genome-wide transcription of Aspergillus nidulans to gain insight into the background of the antifungal activity of this compound. Tyrosol efficiently reduced germination of conidia and the growth on various carbon sources at a concentration of 35 mM.

The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in .

Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron-carbon limitation alters oxidative stress responses, was cultured in glucose-peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after HO treatment.

Global Transcriptomic Changes Elicited by Deletion and Menadione Exposure in .

Manganese superoxide dismutases (MnSODs) play a pivotal role in the preservation of mitochondrial integrity and function in fungi under various endogenous and exogenous stresses. Deletion of mnSOD/SodB increased oxidative stress sensitivity and apoptotic cell death rates as well as affected antioxidant enzyme and sterigmatocystin productions, respiration, conidiation and the stress tolerance of conidiospores. The physiological consequences of the lack of were more pronounced during carbon starvation than in the presence of glucose.

Genome-Wide Gene Expression Analyses of the AtfA/AtfB-Mediated Menadione Stress Response in .

The bZIP transcription factors (TFs) govern regulation of development, secondary metabolism, and various stress responses in filamentous fungi. In this work, we carried out genome-wide expression studies employing Illumina RNAseq to understand the roles of the two bZIP transcription factors AtfA and AtfB in . Comparative analyses of transcriptomes of control, Δ, Δ, and ΔΔ mutant strains were performed.

Stress Responses Elicited by Glucose Withdrawal in .

Glucose is a widely used carbon source in laboratory practice to culture Aspergillus fumigatus, however, glucose availability is often low in its “natural habitats”, including the human body. We used a physiological−transcriptomical approach to reveal differences between A. fumigatus Af293 cultures incubated on glucose, glucose and peptone, peptone (carbon limitation), or without any carbon source (carbon starvation).

Strategies Shaping the Transcription of Carbohydrate-Active Enzyme Genes in .

Understanding the coordinated regulation of the hundreds of carbohydrate-active enzyme (CAZyme) genes occurring in the genomes of fungi has great practical importance. We recorded genome-wide transcriptional changes of cultivated on glucose, lactose, or arabinogalactan, as well as under carbon-starved conditions. We determined both carbon-stress-specific changes (weak or no carbon source vs.

AtfA-Independent Adaptation to the Toxic Heavy Metal Cadmium in .

Cadmium is an exceptionally toxic industrial and environmental pollutant classified as a human carcinogen. In order to provide insight into how we can keep our environment safe from cadmium contamination and prevent the accumulation of it in the food chain, we aim to elucidate how , one of the most abundant fungi in soil, survives and handles cadmium stress. As AtfA is the main transcription factor governing stress responses in , we examined genome-wide expression responses of wild-type and the null mutant exposed to CdCl.

The Negative Effect of Protein Phosphatase Z1 Deletion on the Oxidative Stress Tolerance of Is Synergistic with Betamethasone Exposure.

The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of and was proposed as a potential antifungal drug target.

The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans.

Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance for deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigated functions of the and genes in the model fungus These genes are orthologues of and , which are involved in cytosolic GSH degradation in The deletion of , , or both resulted in a moderate increase in the GSH content in mycelia grown on glucose, reduced conidium production, and disturbed sexual development.

General stress response or adaptation to rapid growth in Aspergillus nidulans?

Genome-wide transcriptional changes in Aspergillus nidulans induced by nine different stress conditions were evaluated to reveal the general environmental stress response gene set showing unidirectional expressional changes under various types of stress. Clustering the genes by their transcriptional changes was a useful technique for identifying large groups of co-regulated genes. Altogether, 1642 co-upregulated and 3916 co-downregulated genes were identified.

Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion.

Background: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the HO-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays.

Intrathalamic connections shape spindle activity - a modelling study.

Spindle oscillations are generated predominantly during sleep state II, through cyclical interactions between thalamocortical and reticular neurons. Inhibition from reticular cells is critical for this activity; it enables burst firing by the de-inactivation of T-type Ca channels. While the effect of different channelopathies on spindling is extensively investigated, our knowledge about the role of intrathalamic connections is limited.

Transcriptome-Based Modeling Reveals that Oxidative Stress Induces Modulation of the AtfA-Dependent Signaling Networks in .

To better understand the molecular functions of the master stress-response regulator AtfA in , transcriptomic analyses of the null mutant and the appropriate control strains exposed to menadione sodium bisulfite- (MSB-), -butylhydroperoxide- and diamide-induced oxidative stresses were performed. Several elements of oxidative stress response were differentially expressed. Many of them, including the downregulation of the mitotic cell cycle, as the MSB stress-specific upregulation of FeS cluster assembly and the MSB stress-specific downregulation of nitrate reduction, tricarboxylic acid cycle, and ER to Golgi vesicle-mediated transport, showed AtfA dependence.

Effects of hemin, CO, and pH on the branching of Candida albicans filamentous forms.

Morphological transitions of wild-type and oxidative stress-tolerant Candida albicans strains were followed in the RPMI-FBS culture medium at pH values and CO levels characteristic for the anatomical niches inhabited by this opportunistic human pathogen fungus, including the oral cavity as well as the intestinal and vaginal lumens. Selected cultures were also supplemented with hemin modeling bleedings. Germination as well as elongation and branching of hyphae were monitored in the cultures using time-lapse video microscopy.

Core oxidative stress response in Aspergillus nidulans.

Background: The b-Zip transcription factor AtfA plays a key role in regulating stress responses in the filamentous fungus Aspergillus nidulans. To identify the core regulons of AtfA, we examined genome-wide expression changes caused by various stresses in the presence/absence of AtfA using A. nidulans microarrays.

Optimization of triacetylfusarinine C and ferricrocin productions in Aspergillus fumigatus.

Iron is an essential element for all microorganisms. Bacteria and fungi produce versatile siderophores for binding and storing this essential transition metal when its availability is limited in the environment. The aim of the study was to optimize the fermentation medium of Aspergillus fumigatus for siderophore production.

Increased oxidative stress tolerance results in general stress tolerance in Candida albicans independently of stress-elicited morphological transitions.

A selection of tert-butylhydroperoxide (tBOOH)-tolerant Candida albicans mutants showed increased tolerances to 19 different stress conditions. These mutants are characterized by a constitutively upregulated antioxidative defense system and, therefore, adaptation to oxidative stress may play an important role in gaining general stress tolerance in C. albicans.

Towards high-siderophore-content foods: optimisation of coprogen production in submerged cultures of Penicillium nalgiovense.

Background: Fungal siderophores are likely to possess atheroprotective effects in humans, and therefore studies are needed to develop siderophore-rich food additives or functional foods to increase the siderophore uptake in people prone to cardiovascular diseases. In this study the siderophore contents of mould-ripened cheeses and meat products were analysed and the coprogen production by Penicillium nalgiovense was characterised.

Results: High concentrations of hexadentate fungal siderophores were detected in penicillia-ripened Camembert- and Roquefort-type cheeses and also in some sausages.

GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation.

Primary lens epithelial cell (LEC) cultures derived from newborn (P0) and one-month-old (P30) mouse lenses were used to study GABA (gamma-aminobutyric acid) signaling expression and its effect on the intracellular Ca2+ ([Ca2+]i) level. We have found that these cultures express specific cellular markers for lens epithelial and fiber cells, all components of the functional GABA signaling pathway and GABA, thus recapitulating the developmental program of the ocular lens. Activation of both GABA-A and GABA-B receptors (GABAAR and GABABR) with the specific agonists muscimol and baclofen, respectively induces [Ca2+]i transients that could be blocked by the specific antagonists bicuculline and CGP55845 and were dependent on extracellular Ca2+.

Trehalose overproduction affects the stress tolerance of Kluyveromyces marxianus ambiguously.

A thermotolerant Kluyveromyces marxianus mutant was developed by exposing yeast cultures repeatedly to 48°C incubation temperature, and the strain was characterized with a significantly increased trehalose content. Unexpectedly, the strain was sensitive to alcohol, osmotic and oxidative stress, which correlated with the increases in the trehalose concentrations. Intracellular glutathione levels declined in both wild-type and mutant cells when exposed to elevating incubation temperatures.

GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+).

Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca(2+))-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise.

Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus.

Major aspects of temporal lobe epilepsy (TLE) can be reproduced in mice following a unilateral injection of kainic acid into the dorsal hippocampus. This treatment induces a non-convulsive status epilepticus and acute lesion of CA1, CA3c and hilar neurons, followed by a latent phase with ongoing ipsilateral neuronal degeneration. Spontaneous focal seizures mark the onset of the chronic phase.

Preconditioning-specific reduction of c-fos expression in hippocampal granule and pyramidal but not other forebrain neurons of ischemic brain: a quantitative immunohistochemical study.

To specify targets for an ischemic preconditioning paradigm (ischemic tolerance), c-fos expressions in ischemic (induced by 10 min bilateral carotid-occlusions subsequent to coagulation of vertebral arteries) and preconditioned rats (treated for 4 min carotid-occlusions 72 h before ischemia) were compared in 12 forebrain areas/nuclei. Fos immunostaining was applied to serial sections of the forebrain and the density (cell number/area measured) of Fos-immunopositive (Fos+) neurons, as well as their percentile changes were determined in five hippocampal and seven extrahippocampal areas/nuclei of ischemic and preconditioned rats. The ratio of counts found in ischemic over control animals showed several fold increase of Fos+ cells in the three layers (granule cell, molecular and polymorphic) of the dentate gyrus, CA3 and CA1 pyramidal neurons, as well as in thalamic and hypothalamic nuclei and limbic cortical areas.