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A PAK-like protein kinase is required for maturation of young hyphae and septation in the filamentous ascomycete Ashbya gossypii.

Filamentous fungi grow by hyphal extension, which is an extreme example of polarized growth. In contrast to yeast species, where polarized growth of the tip of an emerging bud is temporally limited, filamentous fungi exhibit constitutive polarized growth of the hyphal tip. In many fungi, including Ashbya gossypii, polarized growth is reinforced by a process called hyphal maturation. Hyphal maturation refers to the developmental switch from slow-growing hyphae of young mycelium to fast-growing hyphae of mature mycelium. This process is essential for efficient expansion of mycelium. We report for the first time on the identification and characterization of a fungal gene important for hyphal maturation. This novel A. gossypii gene encodes a presumptive PAK (p21-activated kinase)-like kinase. Its closest homolog is the S. cerevisiae Cla4 protein kinase; the A. gossypii protein is therefore called AgCla4p. Agcla4 deletion strains are no longer able to perform the developmental switch from young to mature hyphae, and GFP (green fluorescent protein)-tagged AgCla4p localizes with much higher frequency in mature hyphal tips than in young hyphal tips. Both results support the importance of AgCla4p in hyphal maturation. AgCla4p is also required for septation, indicated by the inability of Agcla4 deletion strains to properly form actin rings and chitin rings. Despite the requirement of AgCla4p for the development of fast-growing hyphae, AgCla4p is not necessary for actin polarization per se, because tips enriched in cortical patches and hyphae with a fully developed network of actin cables can be seen in Agcla4 deletion strains. The possibility that AgCla4p may be involved in regulatory mechanisms that control the dynamics of the actin patches and/or actin cables is discussed.

Actins↗

Cytoplasmic dynein is required to oppose the force that moves nuclei towards the hyphal tip in the filamentous ascomycete Ashbya gossypii.

We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii. For the first time we could demonstrate that the mode of long range nuclear migration consists of oscillatory movements of nuclei with, on average, higher amplitudes in the direction of the growing tip. We could also show that mitotic division proceeds at a constant rate of 0. 64 microm/minute which differs from the biphasic kinetics described for the yeast Saccharomyces cerevisiae. Furthermore we were able to identify the microtubule-based motor dynein as a key element in the control of long range nuclear migration. For other filamentous fungi it had already been demonstrated that inactivating mutations in dynein led to severe problems in nuclear migration, i.e. generation of long nuclei-free hyphal tips and clusters of nuclei throughout the hyphae. This phenotype supported the view that dynein is important for the movement of nuclei towards the tip. In A. gossypii the opposite seems to be the case. A complete deletion of the dynein heavy chain gene leads to nuclear clusters exclusively at the hyphal tips and to an essentially nucleus-free network of hyphal tubes and branches. Anucleate hyphae and branches in the vicinity of nuclear clusters show actin cables and polarized actin patches, as well as microtubules. The slow growth of this dynein null mutant could be completely reverted to wild-type-like growth in the presence of benomyl, which can be explained by the observed redistribution of nuclei in the hyphal network.

Actins↗

Antipruritic and antierythema effects of ascomycete Bulgaria inquinans extract in ICR Mice.

The effect of ethanol extract obtained from Bulgaria inquinans on the scratching behavior and vascular permeability changes induced by compound 48/80, histamine and serotonin in ICR mice was studied. The extract dose-dependently inhibited scratching behavior induced by compound 48/80 and serotonin. A significant inhibition was observed at doses of 300 and 600 mg/kg when Bulgaria inquinans extract was administered orally. However, no inhibitory effect was observed on the histamine-induced scratching behavior by the extract, even at a dose of 600 mg/kg. In addition, it also inhibited the increase in the vascular permeability induced by compound 48/80 and serotonin at doses of 300 and 600 mg/kg; however, it failed to inhibit the increased vascular permeability induced by histamine, even at a dose of 600 mg/kg. Bulgaria inquinans extract showed a potent inhibitory effect on histamine release induced by compound 48/80. These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin.

Administration, Oral↗

Nine constituents including six xanthone-related compounds isolated from two ascomycetes, Gelasinospora santi-florii and Emericella quadrilineata, found in a screening study focused on immunomodulatory activity.

Five metabolites tentatively called GS-1 (1)-5 (5) from Gelasinospora santi-florii, and four tentatively called EQ-4 (6), EQ-6 (7)-8 (9) together with 1-4 from Emericella quadrilineata have been isolated in a screening study on immunomodulatory fungal constituents. Among these nine metabolites, EQ-7 and 8 have been unknown. This time, the structures of GS-4 which has previously been isolated, EQ-7, and -8 have been determined to be (4R,4aS,9aR)-1,9a-dihydronidulalin A (4), (4S,4aR,9aR)-4a-carbomethoxy-1,4,4a,9a-tetrahydro-4,8-dihydroxy-6-methylxanthone (8), and 9-hydroxymicroperfuranone (9), respectively, and the six other metabolites have been identified. On bioassay, a dihydroxanthone, nidulalin A (1), a hexaketide, sordarial (5), and a xanthone, pinselin (7) have displayed significant immunosuppressive activities. The structure-activity relationships of these constituents have also been discussed.

Animals↗

14-epidihydrocochlioquinone B and 14-epicochlioquinone B, antibiotics from fermentations of the ascomycete Neobulgaria pura: structure elucidation and effects on platelet aggregation.

14-Epicochlioquinone B (1) and 14-epidihydrocochlioquinone B (2) were isolated from submerged cultures of Neobulgaria pura (Pers. ex Fr.) Petrak. 14-Epicochlioquinone B is a potent inhibitor of human and bovine platelet aggregation stimulated by different inducers. 14-Epidihydrocochlioquinone B does not inhibit the aggregation of platelets. In addition, both 1 and 2 exhibited cytotoxic and antimicrobial activities.

Animals↗

Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. III. Production of novel isocoumarin derivatives, isolation, and biological activities.

During investigations on the influence of CaBr2 on the secondary metabolism of Lachnum papyraceum, the production of mycorrhizins and lachnumon type antibiotics was strongly inhibited in bromide-containing culture media. Instead, six isocoumarin derivatives, 6-hydroymellein (6), 4-chloro-6-hydroxymellein (7), 4-bromo-6-hydroxymellein (9), 6-methoxymellein (10). 4-chloro-6-methoxymellein (11), and 4-chloro-6,7-dihydroxymellein (12) were isolated. Compounds 7, 9, 11, and 12 have never been isolated from natural sources. 6-Hydroxymellein has been isolated previously from many sources including Gilmaniella humicola and proposed to be a precursor of mycorrhizin A (see reference 6). In comparison to the mycorrhizins, the isocoumarin derivatives exhibited only weak antimicrobial, cytotoxic, phytotoxic, and nematicidal activities.

Animals↗

S19159, a modulator of neurite outgrowth produced by the ascomycete Preussia aemulans. I. Producing strain, fermentation, isolation and biological activity.

A modulator of neurite outgrowth, designated S19159, was isolated from the fermentation broth of fungal strain 19159. This fungus was identified as the loculoascomycete, Preussia aemulans (Rehm) von Arx. In the presence of S19159, the number of neurites extending from the cell bodies of cerebral cortical neurons was markedly reduced. The effect of S19159 was observed specifically in neurons from the central nervous system. The compound exhibited similar activities on cultured cortical, hippocampal and cerebeller neurons but was without detectable effect on dorsal root ganglion neurons and PC12 cells.

Animals↗

Aniptodera indica, a new species of mangrove inhabiting ascomycete from west coast of India.

On decomposing mangrove leaves and woods collected from west coast of India, a new species of Aniptodera was encountered. Aniptodera indica sp. nov. differs from other members of the genus, as the ascospores possess single polar appendage. This new species is described, illustrated and compared with closely resembling species: Aniptodera chesapeakensis and A. juncicola.

Animals↗