Evidence for amphithallism and broad geographical hybridization potential among Agaricus subrufescens isolates from Brazil, France, and Thailand.

Agaricus subrufescens is a cultivated edible and medicinal mushroom. Its known geographical distribution encompasses the Americas, Europe, Oceania, and Asia. The objective of this study was to assess mating compatibility and interfertility of strains originating from Brazil, France, and Thailand. Progeny of each strain were analyed with codominant molecular markers. Multilocus genotype tests revealed that the three strains were amphithallic with percentages of heterokaryotic single spore progenies of 75% for the Thai strain and around 40% for the Brazilian and French strains. In mating tests A. subrufescens had a multiallelic unifactorial system of sexual incompatibility. The three parent strains were interfertile based on experimental pairings of single-spore isolates, the recovery of hybrid heterokaryons from compatible matings, and the ability of hybrids to produce mushrooms and fertile spores. This biological approach supports the inclusion of the European strains within the species and the extension of the geographical distribution range to Asia. Our data should help to develop breeding strategies and to better manage and exploit the diversity existing in A. subrufescens.

The beneficial effect of suramin on monocrotaline-induced pulmonary hypertension in rats.

BACKGROUND: Pulmonary hypertension (PH) is a progressive disorder characterized by an increase in pulmonary artery pressure and structural changes in the pulmonary vasculature. Several observations indicate that growth factors play a key role in PH by modulating pulmonary artery smooth muscle cell (PA-SMC) function. In rats, established monocrotaline-induced PH (MCT-PH) can be reversed by blocking platelet-derived growth factor receptors (PDGF-R), epidermal growth factor receptors (EGF-R), or fibroblast growth factor receptors (FGF-R). All these receptors belong to the receptor tyrosine kinase (RTK) family. METHODS AND RESULTS: We evaluated whether RTK blockade by the nonspecific growth factor inhibitor, suramin, reversed advanced MCT-PH in rats via its effects on growth-factor signaling pathways. We found that suramin inhibited RTK and ERK1/2 phosphorylation in cultured human PA-SMCs. Suramin inhibited PA-SMC proliferation induced by serum, PDGF, FGF2, or EGF in vitro and ex vivo. Treatment with suramin from day 1 to day 21 after monocrotaline injection attenuated PH development, as shown by lower values for pulmonary artery pressure, right ventricular hypertrophy, and distal vessel muscularization on day 21 compared to control rats. Treatment with suramin from day 21 to day 42 after monocrotaline injection reversed established PH, thereby normalizing the pulmonary artery pressure values and vessel structure. Suramin treatment suppressed PA-SMC proliferation and attenuated both the inflammatory response and the deposition of collagen. CONCLUSIONS: RTK blockade by suramin can prevent MCT-PH and reverse established MCT-PH in rats. This study suggests that an anti-RTK strategy that targets multiple RTKs could be useful in the treatment of pulmonary hypertension.