Systematic design of chemical oscillators using complexation and precipitation equilibria

Concentration oscillations are ubiquitous in living systems, where they involve a wide range of chemical species. In contrast, early in vitro chemical oscillators were all derived from two accidentally discovered reactions based on oxyhalogen chemistry. Over the past 25 years, the use of a systematic design algorithm, in which a slow feedback reaction periodically drives a bistable system in a flow reactor between its two steady states, has increased the list of oscillating chemical reactions to dozens of systems. But these oscillating reactions are still confined to a handful of elements that possess multiple stable oxidation states: halogens, sulphur and some transition metals. Here we show that linking a 'core' oscillator to a complexation or precipitation equilibrium can induce concentration oscillations in a species participating in the equilibrium. We use this method to design systems that produce periodic pulses of calcium, aluminium or fluoride ions. The ability to generate oscillations in elements possessing only a single stable oxidation state (for example, Na+, F-, Ca2+) may lead to reactions that are useful for coupling to or probing living systems, or that help us to understand new mechanisms by which periodic behaviour may arise.     

DNA repair synthesis following exposure of guinea-pig pancreatic slices to methyl-N-nitrosourethane in vitro

Zusammenfassung Nachweis, dass Behandlung mit Methyl-n-Nitrosouretan die DNA-Synthese in Gewebeschnitten von Meerschweinchen-Pankreas in vitro induziert.

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This work was supported by the National Cancer Institute Contract No. NOI-CP-23284.     

Reduced fertility in male mice following treatment with niridazole

Zusammenfassung Nach einmaliger i.p.-Injetion von 700 mg/kg Niridazol wurden männiiche Mäuse wiederholt mit unbehandelten Weibchen wöchentlich über 2 Monate hinweg gepaart und die Ova gesammelt. Es konnte eine starke Herabsetzung der Befruchtungsraten 3–4 Wochen nach Paarung festgestellt werden, was die Annahme einer Wirkung auf die meiotische Teilung der Spermatozyten und Spermatiden nahelegt. Nach der 7. Woche trat eine Normalisierung der Fruchtbarkeitsrate ein.

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This work was supported by NIH Grants No. C-6516 and No. FR 05526 and by the Environmental Protection Agency Contract No. CPA-70-17.     

Inhibition of mouse liver protein and nuclear RNA synthesis following combined oral treatment with sodium nitrite and dimethylamine or methylbenzylamine

Zusammenfassung Orale Gabe von Dimethylamin oder Methylbenzylamin zusammen mit Natriumnitrit bewirkte eine synergistische Hemmung der Protein-Synthese in der Leber von Mäusen. Ausserdem hemmte die kombinierte Gabe von Dimethylamin und Nitrit synergistisch die Synthese nuklearer RNS in der Leber.

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Supported by N.I.H. Grants No. C-6516 and No. FR-05526.     

Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease

Hailey-Hailey disease (HHD, MIM 16960) is inherited in an autosomal dominant manner and characterized by persistent blisters and erosions of the skin. Impaired intercellular adhesion and epidermal blistering also occur in individuals with pemphigus (which is due to autoantibodies directed against desmosomal proteins) and in patients with Darier disease (DD, MIM 124200), which is caused by mutations in a gene encoding a sarco/endoplasmic reticulum (ER)-Golgi calcium pump. We report here the identification of mutations in ATP2C1, encoding the human homologue of an ATP-powered pump that sequesters calcium into the Golgi in yeast, in 21 HHD kindreds. Regulation of cytoplasmic calcium is impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient is attenuated in vivo in HHD patients. Our findings not only provide an understanding of the molecular basis of HHD, but also underscore the importance of calcium control to the functioning of stratified squamous epithelia.