Synthetic Studies on 2′-Substituted-4′-thiocytidine Derivatives as Antineoplastic Agents

Abstract

As potential antineoplastic agents, we have synthesized 4′-thioFAC and 4′-thiocytarazid by developing an alternative synthetic method. 4′-ThioFAC showed potent antineoplastic activities in vivo as well as in vitro.     

Ecological traits determine the affinity of birds to a larch plantation matrix,in montane Nagano,central Japan

Although the affinity to the matrix habitat (matrix affinity) determines the fate of species in dynamic landscapes where habitat replacement occurs, only a few studies have examined which ecological traits are associated with matrix affinity. Here, we examined the associations of five ecological traits (i.e., fertility, body weight, migratory behavior, foraging height, and nesting height) with affinity for forest birds to a novel larch plantation matrix habitat. We surveyed the occurrence of birds in larch plantations (matrix habitat) and original deciduous forests (original habitat) in the winter and the breeding season, in a montane region of Nagano prefecture, central Japan. We treated occurrences in the matrix habitat relative to the original habitat as the matrix affinity of each species and examined the associations of ecological traits with matrix affinity, controlling for the relatedness of species. Fertile, resident, and low-nesting species showed high matrix affinity, while an association with body weight was not supported. The associations of foraging groups with matrix affinity were complex. While early successional species showed high matrix affinity, flycatchers had low matrix affinity. The matrix affinity of some foraging groups was greater in the winter than in the breeding season. Based on the results, we predicted that low fertility and migratory, high-nesting species would be sensitive to habitat replacement due to matrix hostility. These predictions may be applicable to other matrix type, region, and taxa.     

Barbiturates suppress glucose utilization by inhibition of hexokinase in neuroblastoma cells.

Exposure to the pentobarbital potently inhibited the 2-deoxy glucose uptake in cultured neuroblastoma cells. The inhibition was assumed to be due to saturation of the uptake in the early stage where the incorporation was linear in the nontreated cells. On the contrary, the incorporation of 3-O-methyl glucose, another glucose analog which is not phosphorylated by hexokinase, was not altered by the treatment with pentobarbital. These results suggest that the suppression of hexokinase is involved in the above-mentioned effect of pentobarbital.     

Multinucleation in mouse fibroblasts cultured in methocel medium

3T3-4E cells formed multinucleate cells with high frequency when incubated in methocel medium. The experiment with hydroxyurea and the cytological observation of mitoses showed that multinucleate cells were produced by nuclear division in the absence of cytokinesis. When transferred onto a solid substratum, most of the multinucleate cells divided within seven hours into mononucleate cells through the process of cytoplasmic division, indicating that cell spreading induced cytokinesis. Other mouse fibroblast lines examined so far showed only the low frequency of multinucleation. These findings indicate that in 3T3-4E cells cultivated in methocel, nuclear division occurred independently of cytokinesis, and that cytokinesis was also anchorage-dependent. This system will be available for studying cytoplasmic division of mammalian cells.     

Spontaneous Structural Changes in Actin Regulate G-F Transformation

Transformations between G- (monomeric) and F-actin (polymeric) are important in cellular behaviors such as migration, cytokinesis, and morphing. In order to understand these transitions, we combined single-molecule Förster resonance energy transfer with total internal reflection fluorescence microscopy to examine conformational changes of individual actin protomers. We found that the protomers can take different conformational states and that the transition interval is in the range of hundreds of seconds. The distribution of these states was dependent on the environment, suggesting that actin undergoes spontaneous structural changes that accommodate itself to polymerization.