Agaricus Bisporus: An assessment of its carcinogenic potency

This assessment focuses on the concentrations of some chemicals present in theAgaricus bisporus mushroom, the cancer-inducing doses of these chemicals or mushroom used in the animal experiments, the total amounts of these chemicals or mushroom needed to induce cancer in these mice, and the estimated total amounts of these chemicals or mushroom needed to induce cancer in humans. By adding the estimated amounts of chemicals needed to induce cancer and by comparing it with the amount of raw mushroom needed to induce the same effect, it becomes obvious that we have accounted for less than 2% of the carcinogenic components of theAgaricus bisporus mushroom. Since some unavailable data handicapped this assessment, it should be regarded as tentative and subject to further adjustment.     

Regulation of Manganese Accumulation and Exchange in Bacillus subtilis W23

An overnight culture of Bacillus subtilis W23 in low-manganese tryptone broth is unable to sporulate and becomes hyperactive with regard to the manganese active transport system during stationary phase. When manganese is added to cells in spent or fresh medium, the cells immediately accumulate a high proportion of the manganese available in the medium. When the hyperactive cells are diluted into broth containing 10 muM Mn(2+), high intracellular manganese levels are reached, and inhibition of ribonucleic acid and protein synthesis occurs. This inhibition is relieved when the intracellular manganese concentration declines to the nontoxic levels characteristic of cells growing in 10 muM Mn(2+). The release of the accumulated manganese is achieved by a reduction in the uptake rate for manganese while the efflux rate remains essentially constant. Inhibitors of ribonucleic acid and protein synthesis prevent the reduction of the high rate of manganese uptake and, therefore, high net concentrations of manganese are maintained in the presence of these inhibitors. The hyperactive manganese uptake system is temperature dependent and inhibited by cyanide and m-chlorophenyl carbonylcyanide hydrazone.     

Mikrurgische und mikrochemische Untersuchung der festen Anthocyankörper im Blütenblatt vonPelargonium zonale

Zusammenfassung Die festen Anthocyanausfällungen im Blütenblatt vonPelargonium zonale Meteor wurden auf ihre physikalischen und chemischen Eigenschaften geprüft.Mit Hilfe des Mikromanipulators konnte festgestellt werden, daß es sich um eine spröde, aber auch irgendwie zähe homogene Masse handelt, die der Nadel ausweicht und, einmal angestochen, in Teilstücke mit zackigem Bruch zerfällt, wobei keine Spur von Farbstoff austritt. Zellsaft von kugellosen Zellen entmischt sich beim Austritt aus der Zelle, während der Zellsaft kugelhältiger Zellen diese Entmischung nicht gibt,Die Frage, ob das feste Anthocyan, abgesehen von seinem Aggregatzustand, mit dem in der Zelle gelösten vollkommen übereinstimmt, muß auf Grund der mikrochemischen Untersuchungen verneint werden. Das Anthocyan der schwarzroten Kugeln zeigt andere chemische Eigenschaften als das im Zellsaft gelöste.Das Verhalten der Kugeln in HNO₃ und Millons Reagens läßt annehmen, daß das Anthocyan hier an einen eiweißreichen Grundkörper gebunden ist. Man könnte dann auch in diesem Falle wie beiGunnera undErythraea von Anthocyanophoren sprechen.     

Regulated degradation of yeast ornithine decarboxylase.

Ornithine decarboxylase (ODC) declines in cells that accumulate an excess of polyamines, the downstream products of the enzyme. Superfluous production of polyamines is thus prevented. In animal cells, polyamines reduce ODC activity by accelerating its degradation. Similar down-regulation of ODC activity has been observed in the budding yeast Saccharomyces cerevisiae, but induced degradation has not been documented. Here we show using pulse-chase analysis that the loss of enzyme activity is the result of increased degradation of ODC. Polyamines reduce the half-life of the newly synthesized protein from 3 h to approximately 10 min. Degradation of bulk ODC pools is also accelerated by polyamines, but the absolute rate of turnover is slower, with a half-life of 5 h in untreated and 1 h in treated cells. Newly synthesized ODC polypeptide thus undergoes a process of maturation that renders it relatively resistant to both basal and polyamine-induced degradation. Proteasome mutants have a blunted or absent regulatory response, implicating both the core protease and the regulatory cap of the proteasome in induced degradation of yeast ODC.     

Adaptive Changes in Postsynaptic Dopamine Receptors Despite Unaltered Dopamine Dynamics in Mice Lacking Monoamine Oxidase B

Monoamine oxidase (MAO) B is considered a key enzyme in dopamine metabolism. The present studies, conducted in MAO B knockout mice, show that lack of MAO B does not alter extracellular levels of dopamine in striatum. Similarly, the synthesis, storage, uptake, and release of dopamine are also unaltered. However, autoradiography revealed a significant up-regulation of the D2-like dopamine receptors in the striatum of MAO B knockout mice. Mutant mice also exhibit a functional supersensitivity of D1-dopamine receptors in the nucleus accumbens. Thus, the agonist SKF 38,393-induced c-Fos immunoreactivity was significantly increased in knockout mice as compared with wild-type controls. In view of the apparently normal basal dopamine dynamics observed in MAO B knockout mice, we hypothesize that a dopamine-independent mechanism underlies adaptations in dopamine receptor function that occur as a consequence of MAO B depletion. Finally, these findings suggest that chronic administration of MAO inhibitors, as occurs in the treatment of Parkinson's disease and depression, may be associated with an increased responsiveness of CNS neurons to dopamine receptor ligands.     

Structural definition of the C5a C terminus by two-dimensional nuclear magnetic resonance spectroscopy

The serum glycoprotein C5a, which is derived from the proteolytic cleavage of complement protein C5, has been implicated in the pathogenesis of a number of inflammatory and allergic conditions. Because C5a induces an inflammatory response upon binding to a specific receptor, structural and mutagenesis studies were carried out to gain a better understanding of this binding interaction. These studies led to the first structural definition of the C terminus of recombinant human (rh)-C5a, determined by two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Our results show that the C terminus adopts an α-helical conformation spanning residues 69 to 74, while the core domain exists as an antiparallel α-helical bundle. This C-terminal helix is connected to the core by a short loop that orients Arg 74 adjacent to Arg 62. Point mutation analysis had already revealed that residues 62 and 74 significantly contribute to agonist activity and receptor binding. Correlation of the C5a tertiary structure with mutational analyses clarifies the significance of the functional and binding properties of Arg 62 and suggests that both Arg 62 and Arg 74 interact at the same binding site on the receptor. Proteins 28:261–267, 1997 © 1997 Wiley-Liss Inc.     

Crystal structure of a DinB family error-prone DNA polymerase from Sulfolobus solfataricus.

A new group of error-prone DNA polymerases overcomes the blockage posed to normal DNA replication by damaged template bases, suggesting an active site with a loose, flexible pocket that accommodates aberrant DNA structures. We have determined a 2.8 A resolution crystal structure of the Sulfolobus solfataricus Dbh protein, a DNA translesion polymerase closely related to Escherichia coli DNA polymerase IV and human polymerase kappa. A high error rate is observed for the Dbh polymerase in a range of 10(-2)-10(-3) for all 12 base substitution mispairs. The crystal structure of Dbh reveals an overall architecture resembling other DNA polymerases but has unique features that are likely to contribute to error-prone synthesis, including -1 frameshifting mutations.     

Über die Entwicklung der Arbeits- und Erregungsleitungsmuskulatur des Herzens von Ratte und Meerschweinchen

Zusammenfassung Die Chemodifferenzierung der Herzmuskulatur von Ratte (215 Tiere) und Meerschweinchen (180 Tiere) wird untersucht und zur Morphodifferenzierung und elektrophysiologisch nachweisbaren Funktionsentwicklung in Beziehung gesetzt. Ferner wird die Entwicklung der Arbeitsmuskulatur mit der des Reizleitungssystems verglichen. Prinzipiell verhält sich die Herzentwicklung bei Ratte und Meerschweinchen ähnlich, doch bestehen erhebliche Unterschiede im Terminplan der Entwicklung. Bei der Ratte erfolgen wesentliche Schritte der Herzentwicklung nach der Geburt, beim Meerschweinchen ist die Entwicklung etwa zur Zeit der Geburt abgeschlossen. In der frühen Embryonalzeit ist die Herzmuskulatur reich an Glykogen, aber arm an Enzymen des oxidativen Stoffwechsels (Bernsteinsäuredehydrogenase, Cytochromoxidase) und -Hydroxibuttersäuredehydrogenase. Kapillaren fehlen. Dann — bei der Ratte etwa ab 12. Embryonaltag — beginnt der Glykogenbestand der Arbeitsmuskulatur abzunehmen. Zunächst werden die subepikardial gelegenen Schichten betroffen. Von hier schreitet die Glykogenverminderung nach innen fort. In den glykogenarm gewordenen Zonen vermehrt sich der Bestand an Atmungsfermenten und Kapillaren. Die Chemodifferenzierung in der Kammermuskulatur erfolgt grundsätzlich von außen nach innen. Parallel hierzu verläuft die Strukturentwicklung der Herzmuskelzellen und es kommt zu elektrophysiologisch nachgewiesenen Änderungen in der Permeabilität der Herzmuskelzellmembranen. Abgeschlossen ist die Entwicklung bei der Ratte nach färberisch-lichtmikroskopischen Befunden in der Mitte der 2. Lebenswoche, nach histochemischen Befunden in der 4. Lebenswoche, nach Maßgabe elektrophysiologischer Beobachtungen nach dem 31. Lebenstag. Die Vorhofmuskulatur ist mit Ausnahme frühembryonaler Stadien stets reicher an Glykogen und ärmer an Atmungsfermenten als die Kammermuskulatur. — Das Reizleitungssystem durchläuft eine eigene Entwicklung. Ursprungsgewebe für das Atrioventricularsystem ist der atrioventriculäre Muskelring. Von hieraus wachsen spezifische Fasern in die Kammermuskulatur vor. Sie unterscheiden sich histochemisch von vornherein von der Arbeitsmuskulatur.

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Summary The present study deals with the chemodifferentiation of the cardiac muscle in rats (215 animals) and Guinea pigs (180 animals). The results obtained are compared with the morphological differentiation and the functional development, as determined by electrophysiological methods. Finally, the development of the cardiac muscle is compared with the development of the conducting system. Fundamentally the development as such is the same in rats and Guinea pigs; however, there are striking differences as far as the schedule for the development is concerned. In rats, important steps in the development of the heart take place after birth, where as in Guinea pigs the development is terminated at approximately the time of birth. In the early embryonic stages the cardiac muscle has a high content of glycogen, but it is poor in enzymes of the oxidative metabolism (succinate dehydrogenase, cytochrome oxidase) and -hydroxibutyricaciddehydrogenase. There are no capillaries. Approximately from the 12th embryonic day onwards a decrease of the glycogen content is observed in the cardiac muscle of rats. The first layers to undergo this change are the subepicardial layers. From there it progresses to the innermost layers. The activity of the respiratory enzymes and the number of the capillaries increases in the areas where the glycogen content is now relatively low. On principle the chemodifferentiation of the ventricular mucsle progresses always from the outermost to the innermost layer. The structural development of the cells of the cardiac muscle goes parallel with it; at the same time changes in the permeability of the membranes of cardiac muscle cells are demonstrable by electro-physiological methods. According to light microscopical findings the development in rats is terminated in the middle of the second week of life, according to histochemical findings in the 4th week of life, electrophysiologically after the 31st day of life. It seems to be a rule that apart from the early embryonic stages the auricular muscle is richer in glycogen and poorer in respiratory enzymes than the ventricular muscle. The conducting system has a separate pattern of development. The initial form of the atrioventricular system is the atrio-ventricular muscular ring. From there specific fibres penetrate into the ventricular musculature. Histochemically they are a priori different from the cardiac muscle.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.

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Stipendiatin der Humboldt-Stiftung.

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Frau Prof. Berta Scharrer mit herzlichem Glückwunsch zum 60. Geburtstag gewidmet.