Inversal relationship between basal adenylcyclase activity and maximal degree of stimulation in membranes of red blood cells from rats.

The degree of stimulation of adenylcyclase activity, in membranes from immature red blood cells from rats, brought about by isoprenaline, guanylyl-imidodiphosphate and sodium fluoride is strongly dependent on the basal activity of the enzyme. The inversal relationship between basal activity and the maximal degree of stimulation by (--) isoprenaline, shows an apparent seasonal dependence.     

Über die Wirkung von Ethacrynsäure auf die Energieübertragung in Mitochondrien

Summary Ethacrynic acid, a diuretic drug, inhibits the endergonic reduction of NADP⁺ by NADH in sonic particles from liver, the energy being supplied either by adding ATP or by respiration.     

An Earth-like correspondence between Saturn's auroral features and radio emission

Saturn is a source of intense kilometre-wavelength radio emissions that are believed to be associated with its polar aurorae, and which provide an important remote diagnostic of its magnetospheric activity. Previous observations implied that the radio emission originated in the polar regions, and indicated a strong correlation with solar wind dynamic pressure. The radio source also appeared to be fixed near local noon and at the latitude of the ultraviolet aurora. There have, however, been no observations relating the radio emissions to detailed auroral structures. Here we report measurements of the radio emissions, which, along with high-resolution images of Saturn's ultraviolet auroral emissions, suggest that although there are differences in the global morphology of the aurorae, Saturn's radio emissions exhibit an Earth-like correspondence between bright auroral features and the radio emissions. This demonstrates the universality of the mechanism that results in emissions near the electron cyclotron frequency narrowly beamed at large angles to the magnetic field.     

Methylhydrazine derivatives,a new class of cytotoxic agents

Zusammenfassung Ausgehend von der Beobachtung, dass 1-Methyl-2-benzyl-hydrazin tumorhemmend wirkt, wurden durch systematische Variationen die für diese Wirkung essentiellen Strukturmerkmale festgelegt. Aus einer grösseren Anzahl von Verbindungen wurden 1-Methyl-2-p-(isopropylcarbamoyl)benzyl-hydrazin-hydrochlorid und 1-Methyl-2-p-allophanoylbenzyl-hydrazin-hydrobromid für ausgedehnte experimentelle und klinische Versuche ausgewählt.     

Die Leucinaminopeptidaseaktivität des Rattenharnes nach Verabreichung einer mastzellerschöpfenden Substanz

Summary LAP activity was determined in rat urine under normal conditions and following mast cell depletion by compound 48/80. A statistically significant increase in urinary LAP activity is found after administration of compound 48/80. This increase is due to mast cell depletion and the resulting anaphylactoid reaction.     

Effect of welding parameters on the heat-affected zone of AISI409 ferritic stainless steel

One of the main problems during the welding of ferritic stainless steels is severe grain growth within the heat-affected zone (HAZ). In the present study, the microstructural characteristics of tungsten inert gas (TIG) welded AISI409 ferritic stainless steel were investigated by electron backscattered diffraction (EBSD), and the effects of welding parameters on the grain size, local misorientation, and low-angle grain boundaries were studied. A 3-D finite element model (FEM) was developed to predict the effects of welding parameters on the holding time of the HAZ above the critical temperature of grain growth. It is found that the base metal is not fully recrystallized. During the welding, complete recrystallization is followed by severe grain growth. A decrease in the number of low-angle grain boundaries is observed within the HAZ. FEM results show that the final state of residual strains is caused by competition between welding plastic strains and their release by recrystallization. Still, the decisive factor for grain growth is heat input.     

A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism

Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta. Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales, for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs. Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis. It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class.     

Idealization of the hydrophobic segment of the alkaline phosphatase signal peptide

Proteins secreted by prokaryotic cells are synthesized as precursors containing an amino-terminal extension sequence or signal peptide. Although these signal peptides share little primary sequence homology, recent studies suggest that they function via common pathways during the transport process and that a common element may reside in their secondary structural characteristics. We are investigating the role of an idealized hydrophobic sequence with high potential for alpha-helix formation in the Escherichia coli alkaline phosphatase signal peptide. Here, amino-acid substitutions were made using site-directed mutagenesis to produce a mutant signal sequence containing nine consecutive leucine residues in the hydrophobic core segment. Transport studies with this mutant precursor indicate that mature alkaline phosphatase is correctly targeted to the E. coli periplasm and that processing of the precursor to the mature form of the enzyme is extremely rapid. In contrast, processing is slowed when the mutant signal sequence is lengthened by the insertion of five additional leucine residues and one serine.