Given two organisms, how can one distinguish whether they belong to the same species or not? This might be straightforward for two divergent organisms, but can be extremely difficult and laborious for closely related ones. A molecular marker giving a clear distinction would therefore be of immense benefit. The internal transcribed spacer 2 (ITS2) has been widely used for lowlevel phylogenetic analyses. Case studies revealed that a compensatory base change (CBC) in the helix II or helix III ITS2 secondary structure between two organisms correlated with sexual incompatibility. We analyzed more than 1300 closely related species to test whether this correlation is generally applicable. In 93%, where a CBC was found between organisms classified within the same genus, they belong to different species. Thus, a CBC in an ITS2 sequence-structure alignment is a sufficient condition to distinguish even closely related species.

No abstract

Background: The decision pro-or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism.

The number of mathematical models for biological pathways is rapidly growing. In particular, Boolean modelling proved to be suited to describe large cellular signalling networks. Systems biology is at the threshold to holistic understanding of comprehensive networks. In order to reach this goal, connection and integration of existing models of parts of cellular networks into more comprehensive network models is necessary. We discuss model combination approaches for Boolean models. Boolean modelling is qualitative rather than quantitative and does not require detailed kinetic information. We show that these models are useful precursors for large-scale quantitative models and that they are comparatively easy to combine. We propose modelling standards for Boolean models as a prerequisite for smooth model integration. Using these standards, we demonstrate the coupling of two logical models on two different examples concerning cellular interactions in the liver. In the first example, we show the integration of two Boolean models of two cell types in order to describe their interaction. In the second example, we demonstrate the combination of two models describing different parts of the network of a single cell type. Combination of partial models into comprehensive network models will take systems biology to the next level of understanding. The combination of logical models facilitated by modelling standards is a valuable example for the next step towards this goal.

Platelets are critical for haemostasis and blood clotting. However, since under normal circumstances blood should flow without clotting, its function is regulated via a complex interplay of activating and inhibiting signal transduction pathways. Understanding this network is crucial for treatment of cardiovascular and bleeding diseases. Detailed protein interaction and phosphorylation data are explored to establish a simplified Boolean model of the central platelet cascades. We implemented the model by means of CellNetAnalyzer and showed how different signalling events coalesce into a fully activated system state. Furthermore, we examined the networks' inherent threshold behaviour using the semi-quantitative modelling software SQUAD. Finally, predictions are verified monitoring phosphorylations which mark different activation phases as modelled. The model can also be applied to simulate different pharmacological conditions as they modify node activity (aspirin, clopidogrel, milrinon, iloprost, combination) and is available for further studies. It agrees well with observations. Activatory pathways are diversified to cope with complex environmental conditions. Platelet activation needs several activation steps to integrate over different network subsets, as they are formed by the interplay of activating kinases, calcium mobilization, and the inhibiting cAMP-PKA system. System stability analysis shows two phases: a sub-threshold behaviour, characterized by integration over different activatory and inhibitory conditions, and a beyond threshold phase, represented by competition and shutting down of counter-regulatory pathways. The integrin network and Akt-protein are critical for stable effector response. Dynamic threshold-analysis reveals a dependency of the relative activating input strength necessary to irreversibly engage the system from the absolute inhibitory signal strength.