Macrocyclic proteoglycan mimics. Potent inhibition of cell adhesion by a bundle of chondroitin sulfate chains assembled on the calix[4]resorcarene platform

Tailed calix[4]resorcarene macrocycle (tail=undecyl) can be used as a platform to assemble four glycosaminoglycan polysaccharide chains to give a new type of proteoglycan mimics. A tetra(chondroitin sulfate) derivative thus obtained from the reaction of macrocyclic octaamine and chondroitin sulfate lactone is readily immobilized on a tissue culture plastic (polystyrene) plate and inhibits fibronectin-mediated adhesion of BHK (baby hamster kidney) cells thereon remarkably strongly with 50% inhibition occurring at a 10 ng/mL or 40 pM concentration range.     

Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors

We report herein synthesis of PKCbeta-selective inhibitors possessing the novel pharmacophore of anilino-monoindolylmaleimide. Several compounds of this series exhibited IC50's as low as 50 nM against human PKCbeta2. One of the most potent compounds, 6l, inhibited PKCbeta1 and PKCbeta2 with IC50 of 21 and 5 nM, respectively, and exhibited selectivity of more than 60-fold in favor of PKCbeta2 relative to other PKC isozymes (PKCalpha, PKCgamma, and PKCepsilon).     

TMC-95A, a reversible proteasome inhibitor, induces neurite outgrowth in PC12 cells

TMC-95A has been characterized as a potent proteasome inhibitor that binds to enzymes non-covalently at low nanomolar concentrations. Herein, the neuritogenic activity of TMC-95A in PC12 rat pheochromocytoma cells is reported for the first time. TMC-95A induced a positive neurite initiation of PC12 cells at concentration ranging from 1 to 20 microM.     

GroEL mediates protein folding with a two successive timer mechanism

GroEL encapsulates nonnative substrate proteins in a central cavity capped by GroES, providing a safe folding cage. Conventional models assume that a single timer lasting approximately 8 s governs the ATP hydrolysis-driven GroEL chaperonin cycle. We examine single molecule imaging of GFP folding within the cavity, binding release dynamics of GroEL-GroES, ensemble measurements of GroEL/substrate FRET, and the initial kinetics of GroEL ATPase activity. We conclude that the cycle consists of two successive timers of approximately 3 s and approximately 5 s duration. During the first timer, GroEL is bound to ATP, substrate protein, and GroES. When the first timer ends, the substrate protein is released into the central cavity and folding begins. ATP hydrolysis and phosphate release immediately follow this transition. ADP, GroES, and substrate depart GroEL after the second timer is complete. This mechanism explains how GroES binding to a GroEL-substrate complex encapsulates the substrate rather than allowing it to escape into solution.     

Influence of light on the morphological changes that take place during the development of the <Emphasis Type="Italic">Flammulina velutipes</Emphasis> fruit body

We show that fruit bodies of Flammulina velutipes can be induced in complete darkness after a sharp temperature reduction (23° to 16°C). However, the fruit bodies that form in complete darkness have a long stipe with an undeveloped pileus on the top (pinhead fruit bodies) and are thinner and whiter than the normal fruit bodies which are formed in the light. This finding suggests that F. velutipes fruit bodies cannot mature in complete darkness. However, when we irradiated the fruit bodies that had formed in complete darkness, a pileus developed immediately, and 4 days later the separation between the stipe and the pileus could be observed. Immediately after light exposure, the stipe also thickened and became increasingly pigmented. The stipe elongation was inhibited until 8 days after light exposure, although stipe elongation progressed very quickly thereafter. Basidospores were also visible in the gills 8 days after light exposure. We consider that the basidiospore development is involved in this rapid stipe elongation, which aids the effective dispersal of basidiospores.     

Bambusicolous fungi in Japan (2): <Emphasis Type="Italic">Phialosporostilbe gregariclava</Emphasis>, a new anamorphic fungus from <Emphasis Type="Italic">Sasa</Emphasis>

One new hyphomycete, Phialosporostilbe gregariclava, is described and illustrated based on specimens collected on dead culms of two Sasa species in Hokkaido and Iwate, Japan. This fungus is compared with previously described species of Phialosporostilbe and Nawawia, and its morphological and cultural characteristics are reported.     

<Emphasis Type="Italic">Puccinia calystegiae-soldanellae</Emphasis>, a new rust species on <Emphasis Type="Italic">Calystegia soldanella</Emphasis> from Japan

A rust species on Calystegia soldanella in Japan has been treated as Puccinia convolvuli to date. However, morphological characteristics of specimens on C. soldanella collected from Japan are significantly different from those of specimens on other Calystegia and Convolvulus species from different areas of the world. It is proved by inoculation experiment that the rust on C. soldanella is specific to C. soldanella. Based on these results, Puccinia rust on C. soldanella from Japan is described as a new species, Puccinia calystegiae-soldanellae.