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D Neubert

Publications and source records attributed to D Neubert.

At least 145 records · Page 8Linked to original sources
PubMed1976

Circadian fluctuations in the activity of DNA-dependent RNA polymerases I and II in the nuclei isolated from mouse tissues and the significance for pharmacological and toxicological studies on transcription.

For pharmacological and toxicological studies on the effect of drugs on transcriptional processes the basic fluctuation in activity during a 24-h period must be known. We have measured the activity of nuclear and mitochondrial DNA-dependent RNA polymerases in cell fractions from mice kept under defined dark/light and feeding schedules. The following results have been obtained: 1. Circadian variations in the activity of RNA polymerases are especially pronounced in the nuclei of liver tissue. These changes depend predominantly on feeding habits and they are comparatively independent on the dark/light schedule. A maximum in the activity of nuclear DNA dependent RNA polymerases can be observed shortely after the beginning of the feeding period. 2. The nuclei isolated from other tissues, such as brain, kidney or embryos during the late stage of embryogenesis shown considerably smaller, if any, fluctuations in connection with the feeding habits. These tissues seem to be especially suitable for pharmacological or toxicological studies on transcriptional processes. 3. While both nuclear DNA-dependent RNA polymerases shown a strong dependence on the feeding habits no obvious circadian viriations can be observed in the activity of the DNA-dependent RNA polymerase localized in the mitochondrial fractions of the same tissue. The regulation of these polymerases in different cell compartments apparently occurs quite independently. The conclusions for the design of experiments on induction processes occurring in liver tissues, drawn from the results presented, are discussed.

Animals↗
PubMed1976

In vitro system for toxicological studies on the development of mammalian limb buds in a chemically defined medium.

In organ culture systems using the Trowell setup, morphogenetic differentiation (which largely mimics the development reached in vivo within 2--3 days) can be obtained in limb buds of mouse embryos during a culture period of 6 days. We succeeded in improving the technique and in achieving good differentiation of the limb buds in a chemically defined culture medium from which all additions of the heterologous serum used in previous studies were omitted. With this technique of using a chemically defined medium, the following results were obtained: (1) A high degree of reproducibility can be obtained in the grade of differentiation if the experimental conditions are standardized and limb buds of the same developmental stage (somite stage) are used. (2) The technique is applicable to species other than mice, such as rats and rabbits, however, the results obtained so far are not so satisfactory as those acquired with mouse limb buds. (3) In an attempt to offer some colloid osmotic pressure, macromolecules like polyvinylpyrrolidone (Periston), polydextrans (Macrodex) or polypeptides (Haemaccel) were added to the culture medium. None of these macromolecules had a beneficial effect on the differentiation of the limb buds in vitro; in the case of Macrodex the differentiation was even impaired. (4) In comparison with the development in a serum-containing medium, the results attained with a chemically defined medium are just as good when judged from microscopical and some biochemical studies (total content of DNA, RNA, protein, and protein-bound hydroxyproline in the explants). The applicability of the test system for the evaluation of embryotoxic effects is discussed.

Animals↗
PubMed1976

Activity of nuclear DNA-dependent RNA polymerases in mouse limb buds differentiating in vivo or in organ culture.

1) A method was developed to measure the activity of DNA dependent RNA polymerase reactions I (alpha-amanitin-insensitive) and II (alpha-amanitin-sensitive) in homogenates of very small amounts of tissue. This technique was used to study the activity of these polymerase reactions in limb buds from mouse embryos developing in vivo or in an organ culture system. This culture system allows the morphogenetic differentiation of limb buds in early stages of embryonic development (day 10-11 of gestation greater than or equal to 37 - 45 pairs of somites) from a blastema stage to well recognizable cartilaginous bone analgen. 2) An increase in the activities of both types of RNA polymerases was found to occur in vivo in limb buds on day 12 of gestation when compared with the activity measured on day 11 of gestation. A similar increase with a maximum about 24-48h after initiation of the cultures could be observed in the explants differentiating in organ culture. To our knowledge this is the first time that induction processes proceeding in mammalian embryonic tissues could be correlated with an increased activity of RNA polymerases. 3)A rough estimate shows that the rate of transcription due to RNA polymerase I measured in homogenates or in isolated nuclei (measured with substrate concentrations giving about 80% of the maximal rate) would account for the assumed rate of rRNA synthesis in vivo. The measurement of the RNA polymerase activity in isolated nuclei, thus, may give some information about the transcriptional processes occurring under "physiological" conditions. 4) The mammalian organ culture system presented provides a suitable model for studying embryonic differentiation processes.

Amanitins↗
PubMed1975

Symmetries of genetic code-doublets.

The fact that 64 base triplets code only about 20 essential amino acids implies a strong degeneracy of certain base doublets. It is shown that the set of degenerate base doublets and the set of non-degenerate base doublets are highlly structured. A mathematical formalism is introduced which allows a systematic description of the consequences of an exchange of bases in a doublet. By this formalism it is shown that the two mentioned set have in fact the same structure.

Biological Evolution↗