Sorbic acid stress in Aspergillus niger

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Parents' and children's communication about genetic risk: a qualitative study, learning from families' experiences

Little is known about how parents explain to their children their risk of inheriting a gene that may cause disease in the child or in the child's future progeny. This study explored how genetic risk information is shared between family members and the factors affecting it, to ascertain the implications for children, young people and their parents to inform future service development and provision. A volunteer group of parents, children (8–11 years) and young people (12+ years) in families affected by or at risk of one of six inherited genetic conditions was interviewed. The semi-structured interviews explored the roles of family members, the language used and the self-reported psychological outcomes in a discussion on genetic risk information. The findings were analysed using grounded theory. A total of 33 families participated, which included 79 individuals. Parents often found discussing genetic risk information very difficult and emotionally painful. Discussions were not usually planned and often a major event prompted parents to finally explain genetic risks to their children; however, children usually preferred to learn about the genetic condition gradually throughout childhood. Parents identified a number of challenges they faced related to talking to children, and many thought health professionals should provide more advice to assist them in providing developmentally appropriate information. We therefore conclude that greater emphasis is required in supporting parents and children in discussing genetic risk information throughout their child's development. Open communication about genetic risks throughout childhood seemed to help children and parents cope better and come to terms with the implications of the genetic condition

The Weak-Acid Preservative Sorbic Acid Is Decarboxylated and Detoxified by a Phenylacrylic Acid Decarboxylase, PadA1, in the Spoilage Mold Aspergillus niger▿ †

Resistance to sorbic and cinnamic acids is mediated by a phenylacrylic acid decarboxylase (PadA1) in Aspergillus niger. A. niger ΔpadA1 mutants are unable to decarboxylate sorbic and cinnamic acids, and the MIC of sorbic acid required to inhibit spore germination was reduced by ∼50% in ΔpadA1 mutants

Impact of the unfolded protein response upon genome-wide expression patterns, and the role of Hac1 in the polarized growth, of Candida albicans

International audienceThe unfolded protein response (UPR) regulates the expression of genes involved in the protein secretory pathway and in endoplasmic reticulum (ER) stress in yeasts and filamentous fungi. We have characterized the global transcriptional response of Candida albicans to ER stresses (dithiothreitol and tunicamy-cin) and established the impact of the transcription factor Hac1 upon this response. Expression of C. albicans Hac1, which is the functional homologue of Saccharomyces cerevisiae Hac1p, is predicted to be translationally regulated via an atypical mRNA splicing event during ER stress. C. albicans genes involved in secretion, vesicle trafficking, stress responses and cell wall biogenesis are up-regulated in response to ER stress, and translation and ribosome biogenesis genes are down-regulated. Hac1 is not essential for C. albicans viability, but plays a major role in this stress-related transcriptional response and is required for resistance to ER stress. In addition, we show that Hac1 plays an important role in regulating the morphology of C. albicans and in the expression of genes encoding cell surface proteins during ER stress, factors that are important in virulence of this fungal pathogen

The Weak Acid Preservative Sorbic Acid Inhibits Conidial Germination and Mycelial Growth of Aspergillus niger through Intracellular Acidification

The growth of the filamentous fungus Aspergillus niger, a common food spoilage organism, is inhibited by the weak acid preservative sorbic acid (trans-trans-2,4-hexadienoic acid). Conidia inoculated at 10(5)/ml of medium showed a sorbic acid MIC of 4.5 mM at pH 4.0, whereas the MIC for the amount of mycelia at 24 h developed from the same spore inoculum was threefold lower. The MIC for conidia and, to a lesser extent, mycelia was shown to be dependent on the inoculum size. A. niger is capable of degrading sorbic acid, and this ability has consequences for food preservation strategies. The mechanism of action of sorbic acid was investigated using (31)P nuclear magnetic resonance (NMR) spectroscopy. We show that a rapid decline in cytosolic pH (pH(cyt)) by more than 1 pH unit and a depression of vacuolar pH (pH(vac)) in A. niger occurs in the presence of sorbic acid. The pH gradient over the vacuole completely collapsed as a result of the decline in pH(cyt). NMR spectra also revealed that sorbic acid (3.0 mM at pH 4.0) caused intracellular ATP pools and levels of sugar-phosphomonoesters and -phosphodiesters of A. niger mycelia to decrease dramatically, and they did not recover. The disruption of pH homeostasis by sorbic acid at concentrations below the MIC could account for the delay in spore germination and retardation of the onset of subsequent mycelial growth

Extending serum half-life of albumin by engineering neonatal Fc receptor (FcRn) binding

A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals. This research was originally published in: Journal of Biological Chemistry. © the American Society for Biochemistry and Molecular Biology