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Stefan Schuster

Publications and source records attributed to Stefan Schuster.

At least 19 recordsLinked to original sources

Understanding the roadmap of metabolism by pathway analysis.

The theoretical investigation of the structure of metabolic systems has recently attracted increasing interest. In this chapter, the basic concepts of metabolic pathway analysis are described and various applications are outlined. In particular, the concepts of nullspace and elementary flux modes are explained. The presentation is illustrated by a simple example from tyrosine metabolism and a system describing lysine production in Corynebacterium glutamicum. The latter system gives rise to 37 elementary modes, 36 of which produce lysine with different molar yields. The examples illustrate that metabolic pathway analysis is a useful tool for better understanding the complex architecture of intracellular metabolism, for determining the pathways on which the molar conversion yield of a substrate-product pair under study is maximal, and for assigning functions to orphan genes (functional genomics). Moreover, problems emerging in the modeling of large networks are discussed. An outlook on current trends in the field concludes the chapter.

Animals↗

The predictive start of hunting archer fish: a flexible and precise motor pattern performed with the kinematics of an escape C-start.

Once their shots have successfully dislodged aerial prey, hunting archer fish monitor the initial values of their prey's ballistic motion and elicit an adapted rapid turning maneuver. This allows these fish to head straight towards the later point of catch with a speed matched to the distance to be covered. To make the catch despite severe competition the fish must quickly and yet precisely match their turn and take-off speed to the initial values of prey motion. However, the initial variables vary over broad ranges and can be determined only after prey is dislodged. Therefore, the underlying neuronal circuitry must be able to drive a maneuver that combines a high degree of precision and flexibility at top speed. To narrow down which neuronal substrate underlies the performance we characterized the kinematics of archer fish predictive starts using digital high-speed video. Strikingly, the predictive starts show all hallmarks of Mauthner-driven teleost C-type fast-starts, which have previously not been noted in feeding strikes and were not expected to provide the high angular accuracy required. The high demands on flexibility and precision of the predictive starts do not compromise their performance. On the contrary, archer fish predictive starts are among the fastest C-starts known so far among teleost fish, with peak linear speed beyond 20 body lengths s(-1), angular speed over 4500 deg. s(-1), maximum linear acceleration of up to 12 times gravitational acceleration and peak angular acceleration of more than 450 000 deg. s(-2). Moreover, they were not slower than archer fish escape C-starts, elicited in the same individuals. Rather, both escapes and predictive starts follow an identical temporal pattern and all kinematic variables of the two patterns overlap. This kinematic equivalence strongly suggests that archer fish recruit their C-start escape network of identified reticulospinal neurons, or elements of it, to drive their predictive starts. How the network drives such a rather complex behavior without compromising speed is a wide open question.

Acceleration↗

TassDB: a database of alternative tandem splice sites.

Subtle alternative splice events at tandem splice sites are frequent in eukaryotes and substantially increase the complexity of transcriptomes and proteomes. We have developed a relational database, TassDB (TAndem Splice Site DataBase), which stores extensive data about alternative splice events at GYNGYN donors and NAGNAG acceptors. These splice events are of subtle nature since they mostly result in the insertion/deletion of a single amino acid or the substitution of one amino acid by two others. Currently, TassDB contains 114 554 tandem splice sites of eight species, 5209 of which have EST/mRNA evidence for alternative splicing. In addition, human SNPs that affect NAGNAG acceptors are annotated. The database provides a user-friendly interface to search for specific genes or for genes containing tandem splice sites with specific features as well as the possibility to download large datasets. This database should facilitate further experimental studies and large-scale bioinformatics analyses of tandem splice sites. The database is available at http://helios.informatik.uni-freiburg.de/TassDB/.

Alternative Splicing↗

Metatool 5.0: fast and flexible elementary modes analysis.

SUMMARY: Elementary modes analysis is a powerful tool in the constraint-based modeling of metabolic networks. In recent years, new approaches to calculating elementary modes in biochemical reaction networks have been developed. As a consequence, the program Metatool, which is one of the first programs dedicated to this purpose, has been reimplemented in order to make use of these new approaches. The performance of Metatool has been significantly increased and the new version 5.0 can now be run inside the GNU octave or Matlab environments to allow more flexible usage and integration with other tools. AVAILABILITY: The script files and compiled shared libraries can be downloaded from the Metatool website at http://pinguin.biologie.uni-jena.de/bioinformatik/networks/index.html. Metatool consists of script files (m-files) for GNU octave as well as Matlab and shared libraries. The scripts are licensed under the GNU Public License and the use of the shared libraries is free for academic users and testing purposes. Commercial use of Metatool requires a special contract.

Computer Simulation↗

Animal cognition: how archer fish learn to down rapidly moving targets.

In extremely rapid maneuvers, animals including man can launch ballistic motor patterns that cannot immediately be corrected. Such patterns are difficult to direct at targets that move in three-dimensional space, and it is presently unknown how animals learn to acquire the precision required. Archer fish live in groups and are renowned for their ballistic hunting technique in which they knock down stationary aerial insect prey with a precisely aimed shot of water. Here we report that these fish can learn to release their shots so as to hit prey that moves rapidly at great height, a remarkable accomplishment in which the shooter must take both the target's three-dimensional motion as well as that of its rising shot into account. To successfully perform in the three-dimensional task, training with horizontal motion suffices. Moreover, all archer fish of a group were able to learn the complex sensomotor skill from watching a performing group member, without having to practice. This instance of social learning in a fish is most remarkable as it could imply that observers can "change their viewpoint," mapping the perceived shooting characteristics of a distant team member into angles and target distances that they later must use to hit.

Animals↗

Performance evaluation of algorithms for SAW-based temperature measurement.

Whenever harsh environmental conditions such as high temperatures, accelerations, radiation, etc., prohibit usage of standard temperature sensors, surface acoustic wave-based temperature sensors are the first choice for highly reliable wireless temperature measurement. Interrogation of these sensors is often based on frequency modulated or frequency stepped continuous wave-based radars (FMCW/FSCW). We investigate known algorithms regarding their achievable temperature accuracy and their applicability in practice. Furthermore, some general rules of thumb for FMCW/FSCW radar-based range estimation by means of the Cramer-Rao lower bound (CRLB) for frequency and phase estimation are provided. The theoretical results are verified on both simulated and measured data.

Acoustics↗

Hunting archer fish match their take-off speed to distance from the future point of catch.

Archer fish can shoot down insect prey with a sharp jet of water. Fish usually fire from positions that are not directly below their target so that a dislodged insect falls ballistically with a horizontal velocity component. Only 100 ms after the insect is on its path both the shooter and other school members can initiate a rapid turn and then head straight in the direction of the later point of impact of their falling prey. The quick turn and subsequent take-off are performed ;open-loop', based on the initial values of the falling insect's motion. We report here that archer fish can not only take off in the direction of the later point of impact but also predict its distance. Distance information allows the fish to adjust their take-off speed so that they would arrive within a narrow time slot slightly (about 50 ms) after their prey's impact, despite large differences in the size of the aligning turn and in the distance to be covered. Selecting a constant speed program with matched speed and catching the insect on the move minimizes frictional losses. The initial speed of starting fish is slightly but systematically too slow and is increased later so that the fish arrive 20 ms earlier than expected and often make the catch on a higher than take-off speed. The variability of later speed changes suggests a systematic ;error' in the take-off, as if the fish underestimated distance. However, this apparent deficiency seems well adapted to the fish catching their prey at a high speed: if later the fish had no possibility to correct an initial error then it is better to start slightly too slow in order to minimize the risk of overshooting the point of catch.

Animals↗

A minimal model for decoding of time-limited Ca2+ oscillations.

Calcium oscillations regulate several cellular processes by activating particular proteins. Most theoretical studies focused on the idealized situation of infinitely long oscillations. Here we analyze information transfer by time-limited calcium spike trains. We show that proteins can be selectively activated in a resonance-like manner by time-limited spike trains of different frequencies, while infinitely long oscillations do not show this resonance phenomenon. We found that proteins are activated more specifically by shorter oscillatory signals with narrower spikes.

Biological Clocks↗

Selective regulation of cellular processes via protein cascades acting as band-pass filters for time-limited oscillations.

We show by mathematical modelling that a two-level protein cascade can act as a band-pass filter for time-limited oscillations. The band-pass filters are then combined into a network of three-level signalling cascades that by filtering the frequency of time-limited oscillations selectively switches cellular processes on and off. The physiological relevance for the selective regulation of cellular processes is demonstrated for the case of regulation by time-limited calcium oscillations.

Calcium Signaling↗

Theoretical model of the interactions between Ca2+, calmodulin and myosin light chain kinase.

Active Ca2+/calmodulin (CaM)-dependent myosin light chain kinase (MLCK) plays an important role in the process of MLC phosphorylation and consecutive smooth muscle contraction. Here, we propose a mathematical model of a detailed kinetic scheme describing interactions among Ca2+, CaM and MLCK and taking into account eight different aggregates. The main model result is the prediction of the Ca2+ dependent active form of MLCK, which is in the model taken as proportional to the concentration of Ca4CaM.MLCK complex. Wegscheider's condition is additionally applied as a constraint enabling the prediction of some parameter values that have not yet been obtained by experiments.

Calcium↗

YANA - a software tool for analyzing flux modes, gene-expression and enzyme activities.

BACKGROUND: A number of algorithms for steady state analysis of metabolic networks have been developed over the years. Of these, Elementary Mode Analysis (EMA) has proven especially useful. Despite its low user-friendliness, METATOOL as a reliable high-performance implementation of the algorithm has been the instrument of choice up to now. As reported here, the analysis of metabolic networks has been improved by an editor and analyzer of metabolic flux modes. Analysis routines for expression levels and the most central, well connected metabolites and their metabolic connections are of particular interest. RESULTS: YANA features a platform-independent, dedicated toolbox for metabolic networks with a graphical user interface to calculate (integrating METATOOL), edit (including support for the SBML format), visualize, centralize, and compare elementary flux modes. Further, YANA calculates expected flux distributions for a given Elementary Mode (EM) activity pattern and vice versa. Moreover, a dissection algorithm, a centralization algorithm, and an average diameter routine can be used to simplify and analyze complex networks. Proteomics or gene expression data give a rough indication of some individual enzyme activities, whereas the complete flux distribution in the network is often not known. As such data are noisy, YANA features a fast evolutionary algorithm (EA) for the prediction of EM activities with minimum error, including alerts for inconsistent experimental data. We offer the possibility to include further known constraints (e.g. growth constraints) in the EA calculation process. The redox metabolism around glutathione reductase serves as an illustration example. All software and documentation are available for download at http://yana.bioapps.biozentrum.uni-wuerzburg.de. CONCLUSION: A graphical toolbox and an editor for METATOOL as well as a series of additional routines for metabolic network analyses constitute a new user-friendly software for such efforts.

Algorithms↗

Differential regulation of proteins by bursting calcium oscillations--a theoretical study.

Calcium in ionic form is a second messenger connecting several input signals to several target processes in the cell. The question arises how one second messenger can transmit more than one signal simultaneously (bow-tie structure of signalling). Experimental data on calcium dynamics often show patterns of successive low-peak and high-peak oscillatory phases, known as bursting. Here, we propose that bursting calcium oscillations can perform the function of simultaneous transmission of two signals at physiological calcium concentrations, for example, by selective activation of two calcium-binding proteins. This differential regulation by periodic bursting is investigated in a theoretical model. The two proteins are assumed to be activated by calcium, and one of them is assumed to be subject to biphasic regulation due to additional inhibitory binding sites. To explore which characteristics of the complex signal could be responsible for independent regulation of low-peak activated and spike activated targets, different bursting patterns of simplified square pulses are applied. Depending on the change in the bursting pattern, one protein can be gradually activated at a constant level of the other protein's activity, or the two proteins can be activated simultaneously, or one protein can be activated while the other one is deactivated simultaneously. Thus, the two proteins can be regulated virtually independently.

Animals↗

Game-theoretical approaches to studying the evolution of biochemical systems.

Evolutionary optimization has been successfully used to increase our understanding of key properties of biochemical systems. Traditional optimization is, however, often insufficient for gaining deeper insights into the evolution of such systems because usually there is a mutual relationship between the properties optimized by evolution and the properties of the environment. Thus, by evolving towards optimal properties, organisms change their environment, which in turn alters the optimum. Evolutionary game theory provides an appropriate framework for analyzing evolution in such 'dynamic fitness landscapes'. We therefore argue that it is a promising approach to studying the evolution of biochemical systems. Indeed, recent studies have applied evolutionary game theory to key issues in the evolution of energy metabolism.

Evolution, Molecular↗

Adenine and adenosine salvage pathways in erythrocytes and the role of S-adenosylhomocysteine hydrolase. A theoretical study using elementary flux modes.

This article is devoted to the study of redundancy and yield of salvage pathways in human erythrocytes. These cells are not able to synthesize ATP de novo. However, the salvage (recycling) of certain nucleosides or bases to give nucleotide triphosphates is operative. As the salvage pathways use enzymes consuming ATP as well as enzymes producing ATP, it is not easy to see whether a net synthesis of ATP is possible. As for pathways using adenosine, a straightforward assumption is that these pathways start with adenosine kinase. However, a pathway bypassing this enzyme and using S-adenosylhomocysteine hydrolase instead was reported. So far, this route has not been analysed in detail. Using the concept of elementary flux modes, we investigate theoretically which salvage pathways exist in erythrocytes, which enzymes belong to each of these and what relative fluxes these enzymes carry. Here, we compute the net overall stoichiometry of ATP build-up from the recycled substrates and show that the network has considerable redundancy. For example, four different pathways of adenine salvage and 12 different pathways of adenosine salvage are obtained. They give different ATP/glucose yields, the highest being 3:10 for adenine salvage and 2:3 for adenosine salvage provided that adenosine is not used as an energy source. Implications for enzyme deficiencies are discussed.

ADP Ribose Transferases↗

Archer fish learn to compensate for complex optical distortions to determine the absolute size of their aerial prey.

Many animals, including humans, can visually judge the absolute size of objects regardless of changes in viewing distance and thus despite the resulting dramatic differences in the size of the actual retinal images. For animals that have to judge the size of aerial objects from underwater views, this can be a formidable problem; our calculations show that considerable and strongly viewpoint-dependent corrections are needed to compensate for the effects of light refraction. Archer fish face these optical difficulties because they have to shoot down aerial insects over a wide range of horizontal and vertical distances. We show here that these fish can learn to acquire size constancy with remarkable precision and are thus fully capable of taking complex viewpoint dependency into account. Moreover, we demonstrate that archer fish solve the problem not by interpolating within a set of stored views and distances but by learning the laws that connect apparent size with the fish's relative position to the target. This enables the fish to readily judge the absolute sizes of objects from completely novel views.

Animals↗

Comparison of network-based pathway analysis methods.

Network-based definitions of biochemical pathways have emerged in recent years. These pathway definitions insist on the balanced use of a whole network of biochemical reactions. Two such related definitions, elementary modes and extreme pathways, have generated novel hypotheses regarding biochemical network function. The relationship between these two approaches can be illustrated by comparing and contrasting the elementary modes and extreme pathways of previously published metabolic reconstructions of the human red blood cell (RBC) and the human pathogen Helicobacter pylori. Descriptions of network properties generated by using these two approaches in the analysis of realistic metabolic networks need careful interpretation.

Algorithms↗

Identification of SAW ID-tags using an FSCW interrogation unit and model-based evaluation.

Surface acoustic wave (SAW) devices are well suited for the application as wireless and completely passive identification (ID)-tag. They operate even under harsh environmental conditions, especially under high temperatures. Interrogation units operate similar to conventional radar systems and therefore, have the same resolution restrictions when an inverse fast Fourier transformation (IFFT) is applied. The application of model-based algorithms to the evaluation of identification tags is presented and enhancements in either improved resolution or reduced system bandwidth are shown. Furthermore, optimizations in the coding scheme for reduced tag sizes are discussed, and measured results obtained by a built interrogation unit and fabricated ID-tags for an identification system are shown.

Journal Article↗