Inhibitory control of neural differentiation in mammalian cells

 In Xenopus embryos, a truncated type II activin receptor (Δ1XAR1), capable of blocking signals by several transforming growth factor (TGF)-β family members, can induce neural tissue suggesting neural fate is under inhibitory control. Activin and bone morphogenetic protein 4 (BMP4) can act as neural inhibitors but only BMP4 can induce epidermis in Xenopus ectodermal cells. We have used the pluripotent mouse embryonal carcinoma cell line P19 to examine whether the mechanisms of ectodermal cell fate decisions are conserved among vertebrates. We show that a P19 cell line expressing Δ1XAR1 will differentiate into neurons. In addition, BMP4 inhibits retinoic acid (RA)-induced neural differentiation of P19 cells and induces keratin expression. These results suggest that in mammals as in amphibians neural fate is under inhibitory control and BMP4 can alter ectodermal differentiation. Received: 23 September 1996 / Accepted: 8 January 1997     

Sequence Analysis of a 25-kb Segment in the 17{degrees}-19{degrees} Region of the Bacillus subtilis Chromosome Containing ada Locus

As a part of the Bacillus subtilis genome sequencing project,we have determined a 25-kb sequence covering the 17°–19°region. This region contains 26 complete open reading frames(ORFs) including the alkA and adaA/B operon, which encode genesfor adaptive response to DNA alkylation. A homology search forthe newly identified 21 ORFs revealed that 4 of them exhibita significant similarity to known proteins, e.g., methicillin-resistantStaphylococcus aureus (MRSA) protein homolog, proteins involvedin chloramphenicol resistance, glucosamine synthase and an ABCtransporter protein. The remaining 17 ORFs did not show anysignificant sequence similarities to known gene products inthe database.     

Terpenoids from the seed of platycladus orientalis

Four labdane-type diterpenoids have been isolated from the seed of Platycladus orientalis. Their structures have been elucidated by spectroscopic and chemical methods.     

Sesquiterpene lactones,geranylnerol and tremetone derivatives from Ageratina species

The investigation of two further Ageratina species afforded, in addition to known compounds, some new ones, a germacrolide, a heliangolide, a guaianolide, a geranylnerol derivative and a tremetone derivative.     

Comparison of endogenous gibberellins in roots and shoots of elongating Salix pentandra seedlings

Gibberellins GA₁, GA₈. GA₁₉. GA₂₉. GA₂₀ and GA₅₆ (2-epi-GA₈). were identified by combined gas chromatography-mass spectrometry in root extracts of elongating Salix pentandra L. seedlings. The presence of GA₈ was also demonstrated for the first time in S. pentandra shoots. The levels of GA₁, GA₈, GA₁₉, GA₂₀ in shoot tissue and in roots were estimated by selected ion monitoring. While the amounts of GA₈ and GA₁₉ were similar in both plant parts. the levels of the biologically active GA₁ and its immediate precursor GA₂₀. were found to be much lower in roots than in shoots.     

Catabolism of 4-hydroxybenzoate in Candida parapsilosis proceeds through initial oxidative decarboxylation by a FAD-dependent 4-hydroxybenzoate 1-hydroxylase

Abstract The first two steps in the catabolism of 4-hydroxybenzoate by the ascomycetous yeast Candida parapsilosis CBS604 were investigated. In contrast to the well-known bacterial pathways and to what was previously assumed, metabolism of 4-hydroxybenzoate in C. parapsilosis proceeds through initial oxidative decarboxylation to give 1,4-dihydroxybenzene. This reaction is catalyzed by a NAD(P)H and FAD-dependent 4-hydroxybenzoate 1-hydroxylase. Further metabolism of 1,4-dihydroxybenzene to the ring-fission substrate 1,2,4-trihydroxybenzene is catalyzed by a NADPH-specific FAD-dependent aromatic hydroxylase acting on phenolic compounds. ¹⁹F-NMR experiments with cell extracts and 2-fluoro-4-hydroxybenzoate as the model compound confirm this metabolic pathway and exclude the alternative pathway proceeding through initial 3-hydroxylation followed by oxidative decarboxylation in the second step.     

Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function

Herein, we report the rational design, synthesis and biological evaluation of conjugates consisting of the synthetic retinoid Am580 and biotin connected via a linker moiety. We found that the linking substructure between the retinoid part and the biotin part is critical for retaining the biological activity. Conjugate 4 with a shorter linker showed similar potency to endogenous retinoid ATRA (1) and the parent compound Am580 (2) for neural differentiation of mouse embryotic carcinoma P19 cells, and showed the same pattern of induction of gene expression. It is expected to be useful as a probe for investigations of retinoid function. The design rationale and structure-activity relationship of the linker moiety are expected to be helpful for developing biotin conjugates of other nuclear receptor ligands.