The sterols of two hadromerida sponges

Summary Sterols were extracted and identified from 2 marine sponges,Aaptos aaptos andSuberites domuncula. The sponges contained conventional C₂₆–C₃₀ sterols with a saturated ring system. Minor amounts of cholest-7-en-3-ol and cholesterol were also present. Cholestanol and 24-ethylcholestanol were the major components of the sterol mixtures.We thank Prof. L. Boniforti (Istituto Superiore di Sanità, Roma) for CG-MS analysis, Prof. R. Pronzato (Istituto di Zoologia dell'Università di Genova) for identifying the sponges and A. Senatore for G.C. measurements. This research was supported by grants of Ministero P.I. and C.N.R.     

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy.     

Physical stress and emetine cardiotoxicity

Résumé Nous rapportons ici des expériences sur le cobaye se rapportant à la toxicité de l'émétine pour le cur, en particulier après potentialisations par de exercices de nage.     

Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae

A functional genomics approach has revealed that caveolae/raft-mediated endocytosis is subject to regulation by a large number of kinases. Here we explore the role of some of these kinases in caveolae dynamics. We discover that caveolae operate using principles different from classical membrane trafficking. First, each caveolar coat contains a set number (one 'quantum') of caveolin-1 molecules. Second, caveolae are either stored as in stationary multi-caveolar structures at the plasma membrane, or undergo continuous cycles of fission and fusion with the plasma membrane in a small volume beneath the surface, without disassembling the caveolar coat. Third, a switch mechanism shifts caveolae from this localized cycle to long-range cytoplasmic transport. We have identified six kinases that regulate different steps of the caveolar cycle. Our observations reveal new principles in caveolae trafficking and suggest that the dynamic properties of caveolae and their transport competence are regulated by different kinases operating at several levels.     

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.     

Cytokinin contents and cAMP metabolism during growth ofEscherichia coli

Summary DuringEscherichia coli growth, we found an inverse correlation between free cytokinin content and cAMP level. The rates of synthesis of adenylate-cyclase and cAMP-phosphodiesterase were practically constant.Acknowledgments. This work is supported by a grant of Consiglio Nazionale delle Ricerche, Rome.     

Power frequency electric field induces biological changes in successive generations of mice

Summary Electromagnetic fields arising from the electrical power system are pervasively present in the environment. To help evaluate their public-health risk we raised 3 successive generations of mice in a low-strength, 60-Hz electric field. We found that the field caused an increased mortality in each generation, and, altered body weights in the 3rd generation.This work was supported by the National Institute of Environmental Health Sciences, Department of Health, Education and Welfare, the Environmental Protection Agency, and the Veterans Administration.