A model for the architecture of the hemocyanin from the arthropod Squilla mantis (Crustacea, Stomatopoda)

Squilla mantis hemocyanin is composed of two hexameric subunits but has electron microscopic profiles different from other bis-hexameric hemocyanins, e.g. Astacus and Homarus. We distinguished three different electron microscopic profiles of S. mantis hemocyanin: two sideviews and a topview. These profiles were studied using computer image alignment and correspondence analysis [Van Heel, M. and Frank, J. (1981) Ultramicroscopy 6, 187 - 194]. With the results of this analysis we were able to build a three-dimensional model for the quaternary structure of this hemocyanin. In this model the two hexamers are stacked in such a way that their hexagonal surfaces overlap to about 60% of their width. In the overlap area four subunits are arranged in two different interhexameric pairs, each forming a bridging area between the two hexamers.     

Habitat suitability of the Wadden Sea for restoration of Zostera marina beds

A conceptual model is proposed, describing potential Zostera marina habitats in the Wadden Sea, based on reported data from laboratory, mesocosm and field studies. Controlling factors in the model are dynamics, degree of desiccation, turbidity, nutrients and salinity. A distinction has been made between a higher and a lower zone of potential habitats, each suitable for different morphotypes of Z. marina. The model relates the decline of Z. marina in the Wadden Sea to increased sediment and water dynamics, turbidity, drainage of sediments (resulting in increased degree of desiccation) and total nutrient loads during the twentieth century. The upper and lower delineation of both the higher and the lower zone of potential Z. marina habitats appear to be determined by one or a combination of several of these factors. Environmental changes in one of these factors will therefore influence the borderlines of the zones. The lower zone of Z. marina will be mainly affected by increased turbidity, sediment dynamics, degree of desiccation during low tide and nutrient load. The higher zone will be affected by increases in water and sediment dynamics, desiccation rates and nutrient loads. Potential Z. marina habitats are located above approx. –0.80 m mean sea level (when turbidity remains at the same level as in the early 1990s) in sheltered, undisturbed locations, and preferably where some freshwater influence is present. At locations with a high, near-marine, salinity, the nutrient load has to be low to allow the growth of Z. marina. The sediment should retain enough water during low tide to keep the plants moist. Our results suggest that the return of Z. marina beds within a reasonable time-scale will require not only suitable habitat conditions, but also revegetation measures, as the changes in the environment resulting from the disappearance of Z. marina may impede its recovery, and the natural import of propagules will be unlikely. Furthermore, the lower zone of Z. marina may require a genotype that is no longer found in the Wadden Sea. Received: 26 April 1999 / Received in revised form: 15 October 1999 / Accepted: 16 October 1999     

Solid-phase synthesis of polymyxin B1 and analogues via a safety-catch approach.

As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity.     

Conductance Ratios and Cellular Identity

Recent experimental evidence suggests that coordinated expression of ion channels plays a role in constraining neuronal electrical activity. In particular, each neuronal cell type of the crustacean stomatogastric ganglion exhibits a unique set of positive linear correlations between ionic membrane conductances. These data suggest a causal relationship between expressed conductance correlations and features of cellular identity, namely electrical activity type. To test this idea, we used an existing database of conductance-based model neurons. We partitioned this database based on various measures of intrinsic activity, to approximate distinctions between biological cell types. We then tested individual conductance pairs for linear dependence to identify correlations. Contrary to experimental evidence, in which all conductance correlations are positive, 32% of correlations seen in this database were negative relationships. In addition, 80% of correlations seen here involved at least one calcium conductance, which have been difficult to measure experimentally. Similar to experimental results, each activity type investigated had a unique combination of correlated conductances. Finally, we found that populations of models that conform to a specific conductance correlation have a higher likelihood of exhibiting a particular feature of electrical activity. We conclude that regulating conductance ratios can support proper electrical activity of a wide range of cell types, particularly when the identity of the cell is well-defined by one or two features of its activity. Furthermore, we predict that previously unseen negative correlations and correlations involving calcium conductances are biologically plausible.     

Prediction of sequential antigenic regions in proteins

Prediction of antigenic regions in a protein will be helpful for a rational approach to the synthesis of peptides which may elicit antibodies reactive with the intact protein. Earlier methods are based on the assumption that antigenic regions are primarily hydrophilic regions at the surface of the protein molecule. The method presented here is based on the amino acid composition of known antigenic regions in 20 proteins which is compared with that of 314 proteins [(1978) Atlas of Protein Sequence and Structure, vol. 5, suppl. 3, 363-373]. Antigenicity values were derived from the differences between the two data sets. The method was applied to bovine ribonuclease, the B-subunit of cholera toxin and herpes simplex virus type 1 glycoprotein D. There was a good correlation between the predicted regions and previously determined antigenic regions.     

Leucostasis, an underestimated cause of death in leukaemia

Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply.