(−)-Maalian-5-ol,a new enantiomeric sesquiterpenoid from the liverwortPlagiochila ovalifolia

Summary A new enantiomeric sesquiterpene alcohol named (–)-maalian-5-ol was isolated from the liverwort, and the structure and absolute configuration was determined to be the stereostructureI by chemical and spectral evidence.The authors express their gratitude to Dr H. Inoue, National Science Museum, for identification of the liverwort, and Prof. T. Tokoroyama, Osaka City University, for sending of the data of (–)--maaliene and (+)-selina-5,11-diene. Thanks are also due to the Ministry of Education for financial support of this work.     

cDNA cloning of bovine substance-K receptor through oocyte expression system

The neuropeptide receptors which are present in very small quantities in the cell and are embedded tightly in the plasma membrane have not been well characterized. Mammals contain three distinct tachykinin neuropeptides, substance P, substance K and neuromedin K, and it has been suggested that there are multiple tachykinin receptors. By electrophysiological measurement, we have previously shown that Xenopus oocytes injected with brain and stomach mRNAs faithfully express mammalian substance-P and substance-K receptors, respectively. Here we report the isolation of the cDNA clone for bovine substance-K receptor (SKR) by extending this method to develop a new cloning strategy. We constructed a stomach cDNA library with a cloning vector that allowed in vitro synthesis of mRNAs and then identified a particular cDNA clone by testing for receptor expression following injection of the mRNAs synthesized in vitro into the oocyte system. Because oocytes injected with exogenous mRNAs can express numerous receptors and channels, our new strategy will be applicable in the general molecular cloning of these proteins. The result provides the first indication that the neuropeptide receptor has sequence similarity with rhodopsin-type receptors (the G-protein-coupled receptor family) and thus possesses multiple membrane-spanning domains.     

Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene

The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability. Here we identify the mouse Fbxw7 gene as a p53-dependent tumour suppressor gene by using a mammalian genetic screen for p53-dependent genes involved in tumorigenesis. Radiation-induced lymphomas from p53+/- mice, but not those from p53-/- mice, show frequent loss of heterozygosity and a 10% mutation rate of the Fbxw7 gene. Fbxw7+/- mice have greater susceptibility to radiation-induced tumorigenesis, but most tumours retain and express the wild-type allele, indicating that Fbxw7 is a haploinsufficient tumour suppressor gene. Loss of Fbxw7 alters the spectrum of tumours that develop in p53 deficient mice to include a range of tumours in epithelial tissues such as the lung, liver and ovary. Mouse embryo fibroblasts from Fbxw7-deficient mice, or wild-type mouse cells expressing Fbxw7 small interfering RNA, have higher levels of Aurora-A kinase, c-Jun and Notch4, but not of cyclin E. We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers.     

Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta

Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.     

Cigarette smoke induces DNA single-strand breaks in human cells

Epidemiological evidence suggests that smoking is a major cause of human lung cancer. However, the mechanism by which cigarette smoke induces the cancer remains obscure, although in tobacco carcinogenesis, promotion and/or co-carcinogenesis may have crucial roles. The epidemiological data show that if an individual stops smoking, the risk of his contracting lung cancer increases no further. Moreover, laboratory experiments show that cigarette smoke condensate (CSC) exhibits co-carcinogenic and promoting activities in tumour production and malignant transformation. Clastogenic action is thought to be intimately involved in tumour promotion, and it is therefore interesting that visible chromosome changes such as chromosome aberrations and sister chromatid exchanges are known to be caused by cigarette smoke. However, there has been no previous direct demonstration that cigarette smoke can cause single-strand breaks (SSB) in DNA. Here we report that cigarette smoke induces considerable numbers of DNA SSB in cultured human cells, and that such strand breaks may be ascribed to active oxygen generated from cigarette smoke.     

Jungermanool,a new labdane diol from the liverwort,Jungermannia torticalyx steph

Summary A new diterpenoid named jungermanool was isolated fromJungermannia torticalyx and the structure was found to be labda-8 (17), 14-dien-9, 13-diol by chemical and spectroscopical methods.Chemical constituents fromHepaticae, Part XXIV: Part XXIII,A. Matsuo, H. Nozaki, M. Nakayama, Y. Kushi, S. Hayashi andN. Kamijo, Tetrahedron Lett.1975, 241.The authors wish to express their gratitude to Dr.T. Seki, Department of Botany, Hiroshima University, for the collection and identification of the liverwort.     

The syntheses of axillarin and its related compounds

Zusammenfassung Axillarin (5, 7, 3, 4-Tetrahydroxy-3,6-dimethoxyflavon). 5,3,4-Trihydroxy-3,6,7-trimethoxyflavon und 5,7,3,4-Tetrahydroxy-3,8-dimethoxyflavon wurden synthetisiert.