Worm burdens in schistosome infections

Schistosomiasis, caused by fluke worms of Schistosoma spp, is one of the most common tropical diseases. Despite decades of research and progress towards the control of the disease, many aspects of the dynamics of infection and immunity remain unresolved. There is, in fact, not even an approximate measure of how many worms are harboured by infected humans. Epidemiological, mathematical and biomedical arguments indicate that individual worm burdens in endemic areas number hundreds to thousands of adult schistosomes, instead of the few to dozens generally assumed on the basis of available autopsy data. As Bruno Gryseels and Sake de Vlas here discuss, this hypothesis has important consequences for research and control, as many constants in schistosomiasis research have to be reconsidered.     

Processing of the intron-encoded U16 and U18 snoRNAs: the conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA.

A novel class of small nucleolar RNAs (snoRNAs), encoded in introns of protein coding genes and originating from processing of their precursor molecules, has recently been described. The L1 ribosomal protein (r-protein) gene of Xenopus laevis and its human homologue contain two snoRNAs, U16 and U18. It has been shown that these snoRNAs are excised from their intron precursors by endonucleolytic cleavage and that their processing is alternative to splicing. Two sequences, internal to the snoRNA coding region, have been identified as indispensable for processing the conserved boxes C and D. Competition experiments have shown that these sequences interact with diffusible factors which can bind both the pre-mRNA and the mature U16 snoRNA. Fibrillarin, which is known to associate with complexes formed on C and D boxes of other snoRNAs, is found in association with mature U16 RNA, as well as with its precursor molecules. This fact suggests that the complex formed on the pre-mRNA remains bound to U16 throughout all the processing steps. We also show that the complex formed on the C and D boxes is necessary to stabilize mature snoRNA.     

Loss of the ORF in the SSUrDNA group I intron of one Naegleria lineage.

We have found a Naegleria lineage in which the SSUrDNA contains a group I intron with a length of 375 nucleotides. This is a unique finding because all group I introns detected until now in Naegleria are 1.3 kilobases long and contain an open reading frame coding for 245 amino acids. Sequence data show that the 375 nucleotide-long intron is at the same place in the SSUrDNA as, and is descendant from, the 1.3 kilobase group I intron present in other species of Naegleria. Our data indicate that in one lineage of Naegleria the group I intron lost part of its DNA that is not contributing to the secondary structure but that carries the open reading frame. The amoeboflagellate genus Naegleria contains strains without the intron and strains with the intron, with or without an open reading frame. Therefore, this genus provides a unique opportunity to study the function and evolution of both the group I intron and the open reading frame.     

Synthesis of intraspecific somatic hybrids of Solanum tuberosum: assessments of morphological, biochemical and nematode (Globodera pallida) resistance characteristics

In an attempt to produce novel agronomic traits, a number ofintraspecific somatic hybrid plants have been produced followingleaf mesophyll protoplast fusion between S. tuberosum dihaploidclones PDH 40 (possessing good tuber shape and yield) and PDH417 (possessing resistance to potato cyst nematode, G. pallida).PDH 417 protoplast-derived calli failed to regenerate plantsusing the described culture conditions preventing this parentaltype amongst the mass of regenerated fusion products. Initially,somatic hybrid plants were selected based on differential pigmentationin tuber sprouts and where possible on petal colour. Differentialmobility of patatin bands in electrophoresed tuber extractsfurther confinned hybridity. The intraspecific somatic hybridsalso showed different levels of resistance to G. pallida pathotypesPa2 and Pa3 in the somatic hybrid plants examined. Key words: Somatic hybridization, dihaploids, patatin, nematode resistance, Solanum tuberosum, potato     

Immune network behavior—II. From oscillations to chaos and stationary states

Two types of behavior have been previously reported in models of immune networks. The typical behavior of simple models, which involve B cells only, is stationary behavior involving several steady states. Finite amplitude perturbations may cause the model to switch between different equilibria. The typical behavior of more realistic models, which involve both B cells and antibody, consists of autonomous oscillations and/or chaos. While stationary behavior leads to easy interpretations in terms of idiotypic memory, oscillatory behavior seems to be in better agreement with experimental data obtained in unimmunized animals. Here we study a series of models of the idiotypic interaction between two B cell clones. The models differ with respect to the incorporation of antibodies, B cell maturation and compartmentalization. The most complicated model in the series has two realistic parameter regimes in which the behavior is respectively stationary and chaotic. The stability of the equilibrium states and the structure and interactions of the stable and unstable manifolds of the saddle-type equilibria turn out to be factors influencing the model's behavior. Whether or not the model is able to attain any form of sustained oscillatory behavior, i.e. limit cycles or chaos, seems to be determined by (global) bifurcations involving the stable and unstable manifolds of the equilibrium states. We attempt to determine whether such behavior should be expected to be attained from reasonable initial conditions by incorporating an immune response to an antigen in the model. A comparison of the behavior of the model with experimental data from the literature provides suggestions for the parameter regime in which the immune system is operating.     

Motility and invasive potency of murine T-lymphoma cells: effect of microtubule inhibitors.

ESb and BW-O-Li1 are T-lymphoma cell lines that form metastases in various organs after injection into syngeneic mice. In vitro, both cell lines invade through a fibroblastic monolayer, but ESb cells do so much slower than BW-O-Li1. By the use of Fourier analysis of cell outlines, we can relate this difference in invasiveness to a difference in cell motility: ESb cells do not perform any conspicuous shape change, whereas BW-O-Li1 cells are actively protruding and retracting large pseudopodia. However, the low-motile ESb cells become as motile and deformable as BW-O-Li1 cells when they have eventually invaded under a fibroblastic monolayer. This indicates that ESb cells do have inherent capability for shape change. Treatment of ESb cells with the microtubule disrupting agent nocodazole concomitantly increases their shape change intensity, and their invasion rate through fibroblast monolayers. On the contrary, the microtubule stabilizing drug taxol inhibits both motility and invasion of BW-O-Li1 cells. Our observations suggest that the microtubule network can repress invasion-bound motility of lymphoid cells.