Mitochondria and nuclei move by different mechanisms in Aspergillus nidulans

This is the publisher's version, also available electronically from "http://jcb.rupress.org".We have examined the effects of the antimicrotubule agent benomyl and several mutations on nuclear and mitochondrial movement in germlings of the filamentous fungus Aspergillus nidulans. While, as previously reported, benomyl inhibited nuclear division and movement, it did not inhibit mitochondrial movement. To test the effects of benomyl more rigorously, we germinated two benomyl super-sensitive, beta-tubulin mutants at a benomyl concentration 50-100 times greater than that required to inhibit colony formation completely. Again nuclear division and movement were inhibited, but mitochondrial movement was not. We also examined conditionally lethal beta-tubulin mutations that disrupt microtubule function under restrictive conditions. Nuclear division and movement were inhibited but, again, mitochondrial movement was not. Finally we examined the effects of five heat-sensitive mutations that inhibit nuclear movement but not nuclear division at restrictive temperatures. These mutations strongly inhibited nuclear movement at a restrictive temperature but did not inhibit mitochondrial movement. These data demonstrate that the mechanisms of nuclear and mitochondrial movement in Aspergillus nidulans are not identical and suggest that mitochondrial movement does not require functional microtubules

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer’s disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, while four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and numbers of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau’s normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold

1,1′-[(5-Hy­droxy­methyl-1,3-phenyl­ene)bis­(methyl­ene)]dipyridin-4(1H)-one monohydrate

The asymmetric unit of the title compound, C19H18N2O3, comprises a whole organic dipyridinone mol­ecule plus a water mol­ecule of crystallization. The planes of the pyridinone rings are approximately perpendicular with the plane of the central aromatic ring [dihedral angles = 80.68 (8) and 83.65 (8)°]. The C—O bond of the hy­droxy group subtends an angle of 31.71 (10)° with the plane through the central aromatic ring. The crystal packing is mediated by the presence of several O—H⋯O hydrogen-bonding inter­actions and while the water mol­ecules form a C 2 1(4) chain parallel to the c axis of the unit cell, the pendant hy­droxy groups are engaged in O—H⋯O=C hydrogen bonds described by a C 1 1(12) graph-set motif which runs parallel to the a axis

Self-assembly in solution of a reversible comb-shaped supramolecular polymer

We report a single step synthesis of a polyisobutene with a bis-urea moiety in the middle of the chain. In low polarity solvents, this polymer self-assembles by hydrogen bonding to form a combshaped polymer with a central hydrogen bonded backbone and polyisobutene arms. The comb backbone can be reversibly broken, and consequently, its length can be tuned by changing the solvent, the concentration or the temperature. Moreover, we have proved that the bulkiness of the side-chains have a strong influence on both the self-assembly pattern and the length of the backbone. Finally, the density of arms can be reduced, by simply mixing with a low molar mass bis-urea