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Production of bikaverin and gibberellins by Gibberella fujikuroi started after depletion of the nitrogen source, but not after depletion of phosphate. Despite this similarity, the regulation of both pathways by nitrogen involved two different mechanisms. This conclusion was supported by the fact that the production of bikaverin, in contrast to the gibberellins, was not inhibited by nitrate in a mutant that could not utilize it. The different regulation of both pathways was clearly demonstrated by a mutant that overproduced bikaverin but lacked gibberellins. An optimal bikaverin production required a low pH, with a sharp drop at about pH 5. The syntheses of fungal secondary metabolites, such as bikaverin and gibberellins, are not subject to common regulation, but respond to various combinations of signals, such as nitrogen availability, nitrate and the pH of the medium.  相似文献   

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Background

Leptin, a cytokine-like protein, plays an important role in the regulation of body weight through inhibition of food intake and stimulation of energy expenditure. Leptin circulates in blood and acts on the brain, which sends downstream signals to regulate body weight. Leptin therapy has been successful in treating leptin deficient obese patients. However, high levels of leptin have been observed in more common forms of obesity indicating a state of leptin resistance which limits the application of leptin in the treatment of obesity. If the central effect of leptin could be by-passed and genes which respond to leptin treatment could be regulated directly, new therapeutic targets for the treatment of obesity may be possible. The purpose of this study was to identify genes and subsequent pathways correlated with leptin-mediated weight loss.

Methodology/Principal Findings

We utilized microarray technology to compare hepatic gene expression changes after two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We identified 214 genes that correlate with leptin mediated weight loss. Several biological processes such as mitochondrial metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic processes, carboxylic acid metabolic processes, iron ion binding and glutathione S-transferases were downregulated after leptin administration. In contrast, genes involved in the immune system inflammatory response and lysosomal activity were found to be upregulated. Among the cellular compartments mitochondrion (32 genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly over represented.

Conclusions/Significance

In this study we have identified key molecular pathways and downstream genes which respond to leptin treatment and are involved in leptin-mediated weight loss. Many of these genes have previously been shown to be associated with obesity; however, we have also identified a number of other novel target genes. Further investigation will be required to assess the possible use of these genes and their associated protein products as therapeutic targets for the treatment of obesity.  相似文献   

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The functional elucidation of plant cell wall biosynthesis (CWB) related genes is important for understanding various stress tolerance responses as well as enhancing biomass in plants. Despite their significant role in physiology and growth of the plant, the function of a limited number of CWB related genes have been identified. Major obstacles such as functional redundancy and limited functional information pose challenges in the characterization of CWB genes. Here, a genome-wide analysis of CWB genes using meta-expression data revealed their roles in stress tolerance and developmental processes. The identification of coexpressed CWB genes suggests functional modules for plant cell wall biosynthesis associated with specific tissue types, biotic stress, abiotic stress, and hormone responses. More interestingly, we identified that glycosyl hydrolases are specialized for root and pollen development, glycosyltransferases for ubiquitous function and leaf development, and carbohydrate esterases for pollen development. A T-DNA insertional mutant of OsCESA9 showing internode preferred expression revealed severe dwarfism and a co-expression network analysis of OsCESA9 in oscesa9 mutant suggest downstream pathways for secondary cell wall biosynthesis and DNA repair processes. Data from our studies will facilitate functional genomic studies of CWB genes in rice and contribute to the enhancement of biomass and yield in crop plants.  相似文献   

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