Kakeromamide A,a new cyclic pentapeptide inducing astrocyte differentiation isolated from the marine cyanobacterium Moorea bouillonii

Kakeromamide A (1), a new cyclic pentapeptide encompassing a thiazole ring moiety and a β-amino acid, was isolated from the marine cyanobacterium Moorea bouillonii. Its structure was elucidated by the spectral analysis and the modified Marfey’s method. Compound 1 induced differentiation of neural stem cells into astrocytes at the concentration of 10?µM.     

RU486 inhibits induction of aromatase by dexamethasone via glucocorticoid receptor in cultured human skin fibroblasts

Effects of RU486 on the induction of aromatase by dexamethasone via glucocorticoid receptor were determined using cultured human skin fibroblasts. Competition of [3H]dexamethasone binding to the cytosol receptor was 7 times stronger with RU486 than with dexamethasone. The order of the strength of competition was RU486 greater than dexamethasone greater than betamethasone greater than prednisolone greater than hydrocortisone. RU486 abolished a specific 8.6 S [3H]dexamethasone binding peak in the cytosol, determined using a sucrose density gradient analysis. Dexamethasone markedly induced aromatase and this event was strongly suppressed by RU486, in a dose-dependent manner, in the cultured skin fibroblasts. A linear correlation between the strength of competition and the induction of aromatase of various glucocorticoids was observed. RU486 non-competitively inhibited aromatase induction by dexamethasone determined from a double reciprocal plot of aromatase activity, with respect to [3H]androstenedione concentration in the presence of RU486. These results show that RU486 is a peripheral noncompetitive antiglucocorticoid on aromatase induction by glucocorticoid in human skin fibroblasts and that aromatase induction is a good marker for the biological function of glucocorticoid receptor in human skin fibroblasts.     

Organic anion transporters,OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess

Like mitochondria, peroxisomes produce reactive oxygen species (ROS), compounds which have been implicated to play an important role in many degenerative diseases and aging itself, and an exaggerated ROS production might occur in altered or older organelles. Growing evidence shows that autophagy, a required function in cell housekeeping during fasting, can remove damaged macromolecules, organelles, and membranes selectively. Proliferation of peroxisomes can be enhanced in liver cells by perfluorooctanoic acid (PFOA), which causes a marked increase of the Acyl-CoA oxidase (ACOX) activity and no significant change in urate oxidase (UOX) activity. The administration of antilipolytic drugs to fasted animals was shown to intensify autophagy. Here we tested the hypothesis that autophagy may distinguish and remove older from younger peroxisomes in rat liver. Male Sprague-Dawley rats were given PFOA (150 mg/kg body weight) or vehicle. Animals were sacrificed at different times following PFOA administration, and 3 h after the induction of autophagy with the antilipolytic agent 3,5-dimethyl pyrazole (DMP, 12 mg/kg body weight). The levels of ACOX and UOX activity were measured in the liver tissue. Results showed that autophagy caused a parallel, significant decrease in both enzymes activity in control rats, and that in PFOA-treated rats the effects were different and changed with PFOA time administration. Changes are compatible with the hypothesis that newly formed ACOX-rich peroxisomes are resistant to pexophagy and that sensitivity to pexophagy increases with increasing peroxisomal “age.” In conclusion, there is indirect evidence supporting the hypothesis that autophagy may recognize and degrade older peroxisomes.     

Phylogenetic significance of stylar features in genus Vicia (Leguminosae): an analysis with molecular phylogeny

Tribe Fabeae consists of five genera, Lathyrus (160 spp.), Lens (4–6 spp.), Pisum (2–3 spp.), Vavilovia (monotypic), and Vicia (160 spp.), and shows a diversity in stylar features. At least six different stylar types are known in the tribe. In order to reclassify the tribe at the rank of genus, we tried to discover apomorphies in stylar features using a molecular phylogenetic study. We surveyed internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA of representative species, selected from each group having different types of styles in the tribe. We paid particular attention in sampling to members of Vicia section Vicilla, as stylar features are heterogeneous within this section. Consequently, our sample set included 15 species of section Vicilla, 23 species of other Fabeae, and two species of Trifolieae, which were used as a sister group of Fabeae. Based on our analysis, we found that a laterally compressed style and an abaxially tufted hairy style would be advanced against a dorsiventrally compressed style and an evenly hairy style, respectively, in genus Vicia. The species group, which shares the latter apomorphy, is composed of 56 species and was dispersed into 11 sections of two subgenera in the recent system of genus Vicia. We consider future revision of Fabeae should treat this species group as a single higher taxon.     

A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family

Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity. Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases.     

Demonstration of Antigenic and Genotypic Variation in Orientia tsutsugamushi Which Were Isolated in Japan,and Their Classification into Type and Subtype

A total of 40 strains of Orientia tsutsugamushi (34 isolates from patients and trombiculid mites in Japan, and 6 prototype strains of antigenic variants) were examined for classification based on the reactivities with type-specific monoclonal antibodies in indirect immunofluorescence tests, and on the restriction fragment length polymorphism of a polymerase chain reaction (PCR)-amplified 56-kilodalton type-specific antigenic protein gene. By these methods, several antigenic and genotypic variants were found among the strains, and these variants were classified into types and further into subtypes. These results suggest that there are many variants in O. tsutsugamushi, and the methods used here seem to be useful for the systematic classification of the numerous variants. A strain which may be a new type distinguishable from those identified previously was also found in this study. Furthermore, variety in the degree of pathogenicity in mice related to type and/or subtype classification were observed.     

Temporal contribution of body movement to very long-term heart rate variability in humans

A newly developed, very long-term ( approximately 7 days) ambulatory monitoring system for assessing beat-to-beat heart rate variability (HRV) and body movements (BM) was used to study the mechanism(s) responsible for the long-period oscillation in human HRV. Data continuously collected from five healthy subjects were analyzed by 1) standard auto- and cross-spectral techniques, 2) a cross-Wigner distribution (WD; a time-frequency analysis) between BM and HRV for 10-s averaged data, and 3) coarse-graining spectral analysis for 600 successive cardiac cycles. The results showed 1) a clear circadian rhythm in HRV and BM, 2) a 1/f (beta)-type spectrum in HRV and BM at ultradian frequencies, and 3) coherent relationships between BM and HRV only at specific ultradian as well as circadian frequencies, indicated by significant (P < 0.05) levels of the squared coherence and temporal localizations of the covariance between BM and HRV in the cross-WD. In a single subject, an instance in which the behavioral (mean BM) and autonomic [HRV power >0.15 Hz and mean heart rate (HR)] rhythmicities were dissociated occurred when the individual had an irregular daily life. It was concluded that the long-term HRV in normal humans contained persistent oscillations synchronized with those of BM at ultradian frequencies but could not be explained exclusively by activity levels of the subjects.     

Unique requirements for template primers of DNA polymerase beta from rat ascites hepatoma AH130 cells.

The optimal condition for the rat DNA polymerase beta activity with (rA)n . (dT)12-18 as a template-primer was determined. The activity was remarkably affected by the concentration of the primer, (dT)12-18' and the mixing ratio of (dT)12-18 to (rA)n. DNA polymerase beta requires higher primer concentration (Km = 11.1 microM with respect to 3'-OH of the primer) than DNA polymerase gamma (Km = 0.04 microM) or oncornaviral DNA polymerase (Km = 0.08 microM) and the enzyme represented the maximum activity in the base ratio of 2:1 with (dT)12-18 and (rA)n suggesting the difference in reaction mechanisms of these enzymes. Under the optimized conditions, the specific activity of the near homogeneous preparation of DNA polymerase beta was 1,000,000 units per mg protein.