Oxidative stress response pathways in fungi.

Fungal response to any stress is intricate, specific, and multilayered, though it employs only a few evolutionarily conserved regulators. This comes with the assumption that one regulator operates more than one stress-specific response. Although the assumption holds true, the current understanding of molecular mechanisms that drive response specificity and adequacy remains rudimentary.

The high osmolarity glycerol (HOG) pathway in fungi.

While fungi are widely occupying nature, many species are responsible for devastating mycosis in humans. Such niche diversity explains how quick fungal adaptation is necessary to endow the capacity of withstanding fluctuating environments and to cope with host-imposed conditions. Among all the molecular mechanisms evolved by fungi, the most studied one is the activation of the phosphorelay signalling pathways, of which the high osmolarity glycerol (HOG) pathway constitutes one of the key molecular apparatus underpinning fungal adaptation and virulence.

Repurposing of auranofin and honokiol as antifungals against species and the related fungus .

The slowing-down drug-discovery emphasized the importance of repurposing old drugs. This is particularly true when combating infections caused by therapy-refractory microorganisms, such as species and . Recent studies on responses to oxidative stress underscored the importance of targeting the underlying mechanisms.

Scedosporium boydii CatA1 and SODC recombinant proteins, new tools for serodiagnosis of Scedosporium infection of patients with cystic fibrosis.

Scedosporium species rank the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus. In CF, these fungi may cause various respiratory infections similar to those caused by A. fumigatus, including bronchitis and allergic broncho-pulmonary mycoses.

Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum.

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively.

Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells.

Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S.

Intestinal cell targeting of a stable recombinant Cu-Zn SOD from Cucumis melo fused to a gliadin peptide.

The mRNA encoding full length chloroplastic Cu-Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD.

Geosmithia argillacea: an emerging pathogen in patients with cystic fibrosis.

We report eight cases of airway colonization by Geosmithia argillacea in patients with cystic fibrosis. This filamentous fungus, resembling members of the genera Penicillium and Paecilomyces, was identified by molecular analysis. All patients carried a mutation on each CFTR (cystic fibrosis transmembrane conductance regulator) allele, with at least one copy of the F508del mutation.

Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress.

The potential benefits to health of antioxidant enzymes supplied either through dietary intake or supplementation is still a matter of controversy. The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.

Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity.

The present study was conducted to evaluate in vitro and in vivo the antioxidant and anti-inflammatory properties of a cantaloupe melon (Cucumis melo LC., Cucurbitaceae) extract (CME) selected for its high superoxide dismutase activity. Peritoneal macrophages were pre-activated in vitro with 300 IU of interferon-gamma (IFN-gamma) and were then challenged in culture with IgGl/anti-IgG1 immune complexes (IgG1IC) in presence of various CME extracts.

Wheat gliadin promotes the interleukin-4-induced IgE production by normal human peripheral mononuclear cells through a redox-dependent mechanism.

Increased levels of serum IgE have been described in gliadin-intolerant patients; however, biological mechanisms implicated in this immunoglobulin production remained unknown. In this study, we demonstrated that in vitro crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE production by human peripheral blood mononuclear cells (PBMC), indicating that the biological process related to gliadin intolerance and/or allergy may lead to IgE production in vivo. It was found that crude gliadin and Glilys potentiated, after 13 days of culture in a dose-dependent manner, IL-4-induced IgE production and, to a lesser extent, the IgG production, while they did not affect IgA or IgM productions.

Promoter sequences involved in transforming growth factor beta1 gene induction in HaCaT keratinocytes after gamma irradiation.

Transforming growth factor beta 1 (TGFB1) is a cytokine involved in the development of both acute and late cutaneous radiation syndromes. We previously demonstrated that ionizing radiation induces TGFB1 expression in vivo in pig skin within a few hours. The purpose of the present study was to develop an in vitro human model to identify the mechanisms of this early activation.

Fc-receptor-mediated intracellular delivery of Cu/Zn-superoxide dismutase (SOD1) protects against redox-induced apoptosis through a nitric oxide dependent mechanism.

Background: Using specific antibodies against bovine Cu/Zn-superoxide dismutase (EC 1.15.1.

Immunohistochemical analysis of cerebral cortical and vascular lesions in the primate Microcebus murinus reveal distinct amyloid beta1-42 and beta1-40 immunoreactivity profiles.

Recent reports have shown that amyloid beta deposits in the brains of Alzheimer's disease patients consist mainly of two distinct species of amyloid beta protein (Abeta) with different C-termini, Abeta1-42 (Abeta42) and Abeta1-40 (Abeta40). The nature of the Abeta species in Microcebus murinus brain was investigated immunocytochemically using polyclonal antibodies with clear specificity for the Abeta42 and Abeta40 C-termini. The cortical vascular deposits were immunopositive for both Abeta42 and Abeta40.

Genetic and physical analyses of the centromeric and pericentromeric regions of human chromosome 5: recombination across 5cen.

Human centromeres are poorly understood at both the genetic and the physical level. In this paper, we have been able to distinguish the alphoid centromeric sequences of chromosome 5 from those of chromosome 19. This result was obtained by pulsed-field gel electrophoresis after cutting genomic DNA with restriction endonucleases NcoI (chromosome 5) and BamHI (chromosome 19).

Cloning of the presenilin 2 cDNA and its distribution in brain of the primate, Microcebus murinus: coexpression with betaAPP and Tau proteins.

A 1340-bp cDNA fragment encoding the lemurian presenilin 2 protein (PS2) was isolated from a Microcebus murinus brain cDNA library by PCR using oligonucleotide primers based on the nucleotide sequence of the human gene. Analysis of five isolated clones showed that the sequence encoded a 448-amino-acid open reading frame, 95.5% identical to the human and 93.

Molecular cloning, sequencing, and brain expression of the presenilin 1 gene in Microcebus murinus.

The cDNA encoding the Microcebus murinus presenilin 1 protein (PSI) was cloned by RT-PCR from a brain cDNA library using various combinations of oligonucleotide primers designed on the basis of the human nucleotide sequence. Analysis of five clones isolated from two positive combinations revealed that the deduced open reading frame encodes two protein isoforms of 467 and 463 amino acid residues. The shorter isoform lacked the four residues VRSQ in the N-terminal region and like the 467 amino acid isoform presented 22 substitutions with its human homologue.

Role of nitric oxide in the anti-tumoral effect of retinoic acid and 1,25-dihydroxyvitamin D3 on human promonocytic leukemic cells.

All trans retinoic acid and vitamin D3 derivatives are well known for their antileukemic activity, while the precise mechanism of this effect remains to be clarified. Using human leukemic U937 and THP-1 promonocytic cell lines, we analyzed the effect of all-trans retinoic acid (RA) and/or 1,25-dihydroxyvitamin D3 (VD) on the generation of nitric oxide (NO), a potent antitumoral mediator. U937 cell differentiation with VD or with both RA and VD (RA/VD) correlated with gene transcription and functional expression of inducible nitric oxide synthase (iNOS).

No founder effect in three novel Alzheimer's disease families with APP 717 Val-->Ile mutation. Clerget-darpoux. French Alzheimer's Disease Study Group.

We sequenced exons 16 and 17 of the APP (amyloid precursor protein) gene in 18 unrelated French Alzheimer's disease (AD) patients. These patients had an onset before the age of 60 and belonged to families with autosomal dominant transmission of the disease. We detected the APP 717 Val-->Ile mutation in three out of 18 (16.

beta-Amyloid protein precursor in Microcebus murinus: genotyping and brain localization.

Senile plaques characterized by beta-amyloid protein (A beta) deposits around dystrophic neurites and glial cells are more abundant in the cerebral cortical parenchyma of Alzheimer's disease (AD) patients than in the aged population. Four different mutations in the amyloid precursor protein (APP) gene have been directly involved in a few cases of familial AD with early onset (before 60 years). Previous studies have shown that Microcebus murinus, a nonhuman primate, also develops analogous deposits of A beta in the cortical parenchyma and blood vessel walls in the brain.

Identification of a unique apolipoprotein E allele in Microcebus murinus; ApoE brain distribution and co-localization with beta-amyloid and tau proteins.

This report is devoted to the characterization of the apolipoprotein E (ApoE) in Microcebus murinus. Only one allele homologous to the human ApoE4 allele was evidenced. The distribution of the corresponding ApoE protein in the brain was found in association with the pathological proteins characteristic of Alzheimer's disease (AD).

A large pedigree with early-onset Alzheimer's disease: clinical, neuropathologic, and genetic characterization.

We present clinical, neuropsychological, and neuropathologic data on a large pedigree including 34 subjects with early-onset progressive dementia. The mean (+/- SD) age at onset was 46 +/- 3.5 years and the mean age at death 52.

The meiosis-specific Xmr gene product is homologous to the lymphocyte Xlr protein and is a component of the XY body.

The Xlr (X-chromosome linked, lymphocyte regulated) multigene family was previously found to determine, in the lymphoid cell lineage, the stage-specific expression of a nuclear protein with a primary sequence suggestive of a transcriptional activator function. We report here the characterization of a second functional member of the Xlr gene family that is abundantly transcribed in testis in a tissue-specific and developmentally regulated manner. The protein product of this newly identified gene, called Xmr (Xlr-related, meiosis regulated), is located in the nuclei of spermatocytes, early in the prophase of the first meiotic division, and later becomes concentrated in the XY nuclear subregion where it is in particular associated with the axes of sex chromosomes.