Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it also connected to number of cancers and developmental disorders. Here we apply combined in-vitro in-silico approach investigate the spatio-temporal regulation during early neural differentiation process human progenitors cells (hNPCs), which form new prospect for replacement therapies context neurodegenerative diseases. Experimental measurements indicate second signal mechanism, addition canonical WNT...

Space plays an ever increasing role in cell biological modeling and simulation. This ranges from compartmental dynamics, via mesh-based approaches, to individuals moving continuous space. An attributed, multi-level, rule-based language, ML-Space, is presented that allows integrate these different types of spatial dynamics within one model. The associated simulator combines Gillespie's method, the Next Subvolume Brownian dynamics. simulation reaction diffusion systems as well taking excluded...

The physico-chemical surface design of implants influences the surrounding cells. Osteoblasts on sharp-edged micro-topographies revealed an impaired cell phenotype, function and Ca2+ mobilization. influence edges ridges Wnt/β-catenin pathway in combination with cells’ stress response has not been clear. Therefore, MG-63 osteoblasts were studied defined titanium-coated micro-pillars (5 × 5 µm) vitro silico. MG-63s indicated activated state pathway. β-catenin protein accumulated cytosol...

Simulation experiments are typically conducted repeatedly during the model development process, for example, to revalidate if a behavioral property still holds after several changes. Approaches automatically reusing and generating simulation can support modelers in conducting studies more systematic effective manner. They rely on explicit experiment specifications and, so far, user interaction initiating reuse. Thereby, they constrained reuse of specific setting. Our approach now goes one...

Biophysical stimulation by electric fields can promote bone formation in defects of critical size. Even though, long-term effects alternating on the differentiation osteoblasts are not fully understood. Human pre-osteoblasts were stimulated over 31 days to gain more information about these cellular processes. An field with 0.7 V rms and 20 Hz at two distances was applied viability, mineralization, gene expression, protein release factors analyzed. The viability enhanced during first...

For many biological systems, a variety of simulation models exist. A new model is rarely developed from scratch, but rather revises and extends an existing one. key challenge, however, to decide which might be appropriate starting point for particular problem why. To answer this question, we need identify entities activities that contributed the development model. Therefore, exploit provenance data model, PROV-DM, World Wide Web Consortium and, building on previous work, continue developing...

Workflows are a promising mean to increase the quality of modeling and simulation (M&S) products such as studies models. In exploiting workflows for M&S, requirements arise that need be reflected in structure components workflow supporting framework, WorMS (WORkflows Modeling Simulation). WorMS, we adapt concepts business process scientific workflows. Particular attention is given extensibility flexibility which supported by plug-in based design selecting nets intermediate representation The...

With the increasing size and complexity of models, developing models by composing existing ones becomes more important. We exploit idea reusing simulation experiments individual for composition to automatically generate composed model. First, we illustrate process modeling based on discuss role can play in this process. Our focus is semantic validation explicitly specify experiment specification via a Scala layer, including desired model behavioral properties their required set-ups. Models...

Endocytosis plays a pivotal regulatory role in canonical WNT signaling. Internalization of the low-density lipoprotein receptor-related protein 6 (LRP6) receptor complex can either promote or attenuate signaling, depending on employed internalization pathway. Detailed analysis mechanism LRP6 and its temporal regulation is crucial for understanding different cellular responses to stimulation under varying conditions various cell types. Here, we elucidate mechanisms involved re-evaluate...

Regulation of microRNA (miRNA) expression contributes to a wide range target gene and phenotypes. The miRNA in the liver, central metabolic organ, was examined 209 pigs, integrated with haematological clinical biomarkers overall health, mRNA-target levels single-nucleotide polymorphism (SNP) genotypes. 426 species correlated plasma or biochemical traits ( r ² = |0.19–0.45|, false discovery rate < 5%). Pairs these miRNAs their predicted mRNAs showing expressing associated identical were...

Conceptual models play an important role in conducting simulation studies. A formal or at least explicit specification of conceptual is key for effectively exploiting them during studies and thereafter, interpreting reusing the results. However, perception varies strongly with it possible means specification. broad definition model, i.e., as a loose collection early-stage products study, holds potential to unify existing definitions, but also poses specific challenges To approach these...

Temperature stress is one of the main environmental stressors affecting welfare, health and productivity livestock. changes can modify cell membrane components, disrupting crosstalk between its surroundings by signaling pathways including Wnt pathway, which subsequently disrupts energy metabolism. The present study aims to understand effect temperature on expression genes involved in pathways, their interaction with metabolism C2C12 myoblasts cells. cells were exposed cold (35 °C), mild heat...

It is widely accepted that lipid rafts promote receptor clustering and thereby facilitate signaling transduction. The role of in inducing promoting accumulation within the cell membrane has been explored by several computational experimental studies. However, it remains unclear whether influence recruitment binding proteins from cytosol as well. To provide an answer to this question a spatial model developed based on cellular automata. Our results indicate indeed protein bindings. In...

Developing a model for simulation is an art and science. The question how this process can be suitably supported. Integrating workflows into systems promises user guidance, documentation reproducibility of process. However, the highly interactive, partly concurrent,

Simulation studies are intricate processes in which model building, refinement, and a wide variety of simulation experiments typically closely intertwined to achieve the objective study. To (semi-)automatically support this process, central artifacts study, such as models experiments, need be made explicit accessible. Furthermore, relations between well their context (e.g., objectives, data sources, requirements) have an unambiguous manner. If information is enriched by knowledge about...

Microdomains or lipid rafts greatly affect the distribution of proteins and peptides in membrane play a vital role formation activation receptor/protein complexes. A prominent example for decisive impact on signaling is LRP6, whose localization to same domain as kinase CK1γ crucial its successful phosphorylation subsequent signalosome, hence WNT/β-catenin signaling. However, according various experimental measurements, approximately 25 35 % cell plasma covered by nanoscopic raft domains with...

The liver is the central metabolic organ and exhibits fundamental functions in haematological traits. Hepatic expression, haematological, plasma biochemical, body composition traits were assessed a porcine model (n = 297) to establish tissue-specific genetic variations that influence function of immune-metabolism-correlated expression networks. At FDR (false discovery rate) <1%, more than 3,600 transcripts jointly correlated (r |0.22-0.48|) with Functional enrichment analysis demonstrated...

A decomposition of a molecular conformational space into sets or functions (states) allows for reduced description the dynamical behavior in terms transition probabilities between these states. Spectral clustering corresponding probability matrix can then reveal metastabilities. The more states are used decomposition, smaller risk to cover multiple conformations with one state, which would make indistinguishable. However, since computational complexity algorithm increases quadratically...

With the advance of high-throughput sequencing technology numerous new regulatory small RNAs have been identified, that broaden variety processing mechanisms and functions non-coding RNA. Here we explore RNA (sncRNA) expression in central parts physiological stress anxiety response system. Therefore, characterize sncRNA profile tissue samples from Amygdala, Hippocampus, Hypothalamus Adrenal Gland, obtained 20 pigs. Our analysis reveals all tissues but Amygdala Hippocampus possess distinct,...

Workflows are a promising mean to increase the quality of modeling and simulation (M&S) products such as studies models. In exploiting workflows for M&S, requirements arise that need be reflected in structure components workflow supporting framework, WORMS (WORkflows Modeling Simulation). WORMS, we adapt concepts business process scientific workflows. Particular attention is given extensibility flexibility which supported by plug-in based design selecting nets intermediate representation The...

The molecular basis of porcine coping behavior (CB) relies on a sophisticated interplay genetic and epigenetic features. Deep sequencing technologies allowed the identification plethora new regulatory small non-coding RNA (sncRNA). We characterized mRNA sncRNA profiles central parts physiological stress response system including amygdala, hippocampus, hypothalamus adrenal gland using systems biology for integration. Therefore, ten each high- (HR) low- (LR) reactive pigs ( n = 20) carrying CB...

Multi-level modeling is concerned with describing a system at different levels of organization and relating their dynamics. ML-Rules rule-based language developed for supporting the cell biological systems. It supports nested rule schemata, hierarchical dynamic nesting species, assignment attributes solutions to species each level, flexible definition reaction rate kinetics. As allows compact description rather complex models, means an efficient execution were developed, e.g., approximate...