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Biomedical subjects

P Hogeweg

Publications and source records attributed to P Hogeweg.

8 recordsLinked to original sources
PubMed1992

Equal G and C contents in histone genes indicate selection pressures on mRNA secondary structure.

Protein-specific versus taxon-specific patterns of nucleotide frequencies were studied in histone genes. The third positions of codons have a (well-known) taxon-specific G+C level and a histone type-specific G/C ratio. This ratio counterbalances the G/C ratio in the first and second positions so that the overall G and C levels in the coding region become approximately equal. The compensation of the G/C ratio indicates a selection pressure at the mRNA level rather than a selection pressure or mutation bias at the DNA level or a selection pressure on codon usage. The structure of histone mRNAs is compatible with the hypothesis that the G/C compensation is due to selection pressures on mRNA secondary structure. Nevertheless, no specific motifs seem to have been selected, and the free energy of the secondary structures is only slightly lower than that expected on the basis of nucleotide frequencies.

Animals↗
PubMed1990

Iterative character weighting based on mutation frequency: a new method for constructing phyletic trees.

In this paper we present an iterative character weighting method for the construction of phyletic trees. An initial tree is used to calculate the character weights, which are the number of mutations normalized so that the possible range is corrected for. The weights obtained are used to adjust the tree; this process is iterated until a stable tree is found. Using data generated according to a model tree, we show that the trees constructed by the iterative character weighting method converge to the true underlying tree. Using biological data, the trees become closer to the systematic classification of the species concerned, and patterns conflicting with the phylogenetic pattern can be singled out. The method involves a combination of minimal length methods and similarity methods, whereby the strict parsimony criterion is relaxed.

Animals↗
PubMed1990

Structural analysis of a group II intron by chemical modifications and minimal energy calculations.

Folding of the yeast mitochondrial group II intron aI5c has been analysed by chemical modification of the in vitro synthesised RNA with dimethylsulfate and diethylpyrocarbonate. Computer calculations of the intron secondary structure through minimization of free energy were also performed in order to study thermodynamic properties of the intron and to relate these to data obtained from chemical modification. Comparison of the two sets of data with the current phylogenetic model structure of the intron aI5 reveals close agreement, thus lending strong support for the existence of a typical group II intron core structure comprising six neighbouring stem-loop domains. Local discrepancies between the experimental data and the model structures have been analyzed by reference to thermodynamic properties of the structure. This shows that use of the latest refined set of free energy values improves the structure calculation significantly.

Base Sequence↗
PubMed1989

Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation.

Previous work was concerned with symmetric immune networks of idiotypic interactions amongst B cell clones. The behaviour of these networks was contrary to expectations. This was caused by an extensive percolation of idiotypic signals. Idiotypic activation was thus expected to affect almost all (greater than 10(7] B cell clones. We here analyse whether the incorporation of helper T cells (Th) into these B cell models could cause a reduction in the percolation. Empirical work on idiotypic interactions between Th and B cells however, would suggest that two different idiotypic Th models should be developed: (1) a Th which recognises native B cell idiotypes, i.e. a non-MHC-restricted "ThId" model, and (2) a "classical" MHC-restricted helper T cell model. In the ThId model, the Th-B cell interaction is symmetric. A 2-D model of a Th and a B cell clone that interact idiotypically with each other accounts for various equilibria (i.e. one virgin and two immune states). Introduction of antigen does indeed lead to a state switch from the virgin to the immune state; such a system is thus able to "remember" its exposure to antigen. Idiotypic signals do however, percolate in ThId models via these "B-Th-B-Th" pathways: proliferating Th and B cell clones that interact idiotypically, will always activate each other reciprocally. In the MHC-restricted Th model, Th-B interactions are asymmetric. Because the B cell idiotypes are processed and subsequently presented by MHC molecules, the Th receptor and the native B cell receptor are not expected to be complementary. Thus the Th and the B cells are unable to activate each other reciprocally, and a 2-D Th-B cell model cannot account for idiotypic memory. In contrast to the ThId model, idiotypic activation cannot percolate via "B-Th-B-Th" interactions. Due to the assymmetry idiotypic activation stops at the first Th level. A Th clone cannot activate a subsequent B cell clone: if the B cells recognise the Th cells, they see idiotype but get no help; if the Th cells see the B cells, the B cells are helped but see no idiotype. The percolation along "B-B-B" pathways in these two models is next analysed. Two B cells clones, each helped by one Th clone, are connected by a symmetric idiotypic interaction. It turns out that in both models the second (i.e. anti-idiotypic) B cells (B2) never proliferate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Pattern analysis of RNA secondary structure similarity and consensus of minimal-energy folding.

We describe an automated procedure to search for consensus structures or substructures in a set of homologous or related RNA molecules. The procedure is based on the calculation of optimal and sub-optimal secondary structures using thermodynamic rules for base-pairing by energy-minimization. A linear representation of the secondary structures of the related RNAs is used so that they can be compared and classified using standard alignment and clusterings programs. We illustrate the method by means of two sets of homologous small RNAs, U2 and U3, and a set of alpha-globin mRNAs and show that biologically interesting consensus structures are obtained.

Animals↗
PubMed1989

Local T-T cell and T-B cell interactions: a cellular automaton approach.

In this paper we use cellular automata to study growth factor (IL-2) dependent proliferation of helper T cell (Th) and B cell clones at the level of individual cells. We argue that such a spatially- and individual-oriented approach can provide important insights, not obtainable by more conventional modelling approaches in which the immune system is modelled as a well mixed collection of clones. Two questions are examined: (1) under which conditions can a cell which produces its own growth factor (i.e. Th cells) be regulated by it; and (2) if a growth factor is effective only locally, and if both Th and B cells depend on growth factors excreted by Th cells, how can the spatial segregation of T cells and B cells in lymphoid organs and/or at acute infection sites be explained? The results show that, firstly, autocrine regulation can indeed occur in two ways: it can ensure (a) that the cell reacts only on its growth factor when packed inside tissue of arbitrary cells or (b), that the cell reacts only when close to other growth factor producing cells; and secondly, segregation of T cells and B cells results automatically from simple assumptions about the interaction and proliferation of the cells, notwithstanding the fact that proliferation is slowed down by this segregation.

Animals↗