Fish-Farming and the Precautionary Principle: Context and Values in Environmental Science for Policy

The paper starts with the assumption that the Precautionary Principle (PP) is one of the most important elements of the concept of sustainability. It is noted that PP has entered international treaties and national law. PP is widely referred to as a central principle of environmental policy. However, the precise content of PP remains largely unclear. In particular it seems unclear how PP relates to science. In section 2 of the paper a general overview of some historical and systematic features of PP are presented. In section 3 a specific case is discussed in greater detail. It is claimed that the escape of farmed salmon from fish cages in the Sea, and its eventual invasion of the breeding places of the wild salmon up the rivers, must be regarded a proper case for applying PP. Yet there is no single PP-strategy. Instead, four different strategies are presented, and all of them can be regarded precautionary strategies in the light of PP. The choice between these strategies is based upon personal values. In section 4 of the paper a general analysis is given which relates these different value perspectives to basic differences in risk aversion, which in turn are related to differing conceptions of nature and/or society. In the concluding section 5 some general consequences of the foregoing analysis are outlined.     

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.     

Glucodigifucosid,Neo-Glucodigifucosid und Digitoxigenin-allomethylosid aus den Blättern vonDigitalis lanata Ehrh

Summary The primary glycosides, glucodigifucoside and neo-glucodigifucoside, were isolated from the extract ofDigitalis lanata leaves. They are isomeric glucosides of digiproside and differ in the position of attachment of thed-glucose residue. Digitoxigenin-allomethylosid was isolated from the leaves after enzymatic decomposition.

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23. Mitteilung über Herzglykoside; unter der ausgezeichneten experimentellen Mitarbeit vonH. Gerlach.     

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.     

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.     

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.     

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.