@article{HartungBenaryWolfetal.2017, author = {Hartung, Niklas and Benary, Uwe and Wolf, Jana and Kofahl, Bente}, title = {Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes}, series = {BMC systems biology}, volume = {11}, journal = {BMC systems biology}, publisher = {BioMed Central}, address = {London}, issn = {1752-0509}, doi = {10.1186/s12918-017-0470-9}, pages = {16}, year = {2017}, abstract = {Background: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/beta-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/beta-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. Results: Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/beta-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. Conclusions: Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter-and intracellular processes, such as Dkk feedback, diffusion and Wnt/beta-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression.}, language = {en} } @article{SinnEngbert2016, author = {Sinn, Petra and Engbert, Ralf}, title = {Small saccades versus microsaccades: Experimental distinction and model-based unification}, series = {Vision research : an international journal for functional aspects of vision.}, volume = {118}, journal = {Vision research : an international journal for functional aspects of vision.}, publisher = {Elsevier}, address = {Oxford}, issn = {0042-6989}, doi = {10.1016/j.visres.2015.05.012}, pages = {132 -- 143}, year = {2016}, abstract = {Natural vision is characterized by alternating sequences of rapid gaze shifts (saccades) and fixations. During fixations, microsaccades and slower drift movements occur spontaneously, so that the eye is never motionless. Theoretical models of fixational eye movements predict that microsaccades are dynamically coupled to slower drift movements generated immediately before microsaccades, which might be used as a criterion to distinguish microsaccades from small voluntary saccades. Here we investigate a sequential scanning task, where participants generate goal-directed saccades and microsaccades with overlapping amplitude distributions. We show that properties of microsaccades are correlated with precursory drift motion, while amplitudes of goal-directed saccades do not dependent on previous drift epochs. We develop and test a mathematical model that integrates goal-directed and fixational eye movements, including microsaccades. Using model simulations, we reproduce the experimental finding of correlations within fixational eye movement components (i.e., between physiological drift and microsaccades) but not between goal-directed saccades and fixational drift motion. These results lend support to a functional difference between microsaccades and goal-directed saccades, while, at the same time, both types of behavior may be part of an oculomotor continuum that is quantitatively described by our mathematical model. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @article{KruegelEngbert2014, author = {Kruegel, Andre and Engbert, Ralf}, title = {A model of saccadic landing positions in reading under the influence of sensory noise}, series = {Visual cognition}, volume = {22}, journal = {Visual cognition}, number = {3-4}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1350-6285}, doi = {10.1080/13506285.2014.894166}, pages = {334 -- 353}, year = {2014}, language = {en} } @article{EbenhoehHouwaartLoksteinetal.2011, author = {Ebenhoeh, Oliver and Houwaart, Torsten and Lokstein, Heiko and Schlede, Stephanie and Tirok, Katrin}, title = {A minimal mathematical model of nonphotochemical quenching of chlorophyll fluorescence}, series = {Biosystems : journal of biological and information processing sciences}, volume = {103}, journal = {Biosystems : journal of biological and information processing sciences}, number = {2}, publisher = {Elsevier}, address = {Oxford}, issn = {0303-2647}, doi = {10.1016/j.biosystems.2010.10.011}, pages = {196 -- 204}, year = {2011}, abstract = {Under natural conditions, plants are exposed to rapidly changing light intensities. To acclimate to such fluctuations, plants have evolved adaptive mechanisms that optimally exploit available light energy and simultaneously minimise damage of the photosynthetic apparatus through excess light. An important mechanism is the dissipation of excess excitation energy as heat which can be measured as nonphotochemical quenching of chlorophyll fluorescence (NPQ). In this paper, we present a highly simplified mathematical model that captures essential experimentally observed features of the short term adaptive quenching dynamics. We investigate the stationary and dynamic behaviour of the model and systematically analyse the dependence of characteristic system properties on key parameters such as rate constants and pool sizes. Comparing simulations with experimental data allows to derive conclusions about the validity of the simplifying assumptions and we further propose hypotheses regarding the role of the xanthophyll cycle in NPQ. We envisage that the presented theoretical description of the light reactions in conjunction with short term adaptive processes serves as a basis for the development of more detailed mechanistic models by which the molecular mechanisms of NPQ can be theoretically studied.}, language = {en} }