Publications by authors named "J K Scholma"
A fundamental question in cartilage biology is: what determines the switch between permanent cartilage found in the articular joints and transient hypertrophic cartilage that functions as a template for bone? This switch is observed both in a subset of OA patients that develop osteophytes, as well as in cell-based tissue engineering strategies for joint repair. A thorough understanding of the mechanisms regulating cell fate provides opportunities for treatment of cartilage disease and tissue engineering strategies. The objective of this study was to understand the mechanisms that regulate the switch between permanent and transient cartilage using a computational model of chondrocytes, ECHO.
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- Computational modeling is being used to study complex signaling networks in biology, particularly focusing on cartilage development and osteoarthritis, through a visual-based tool accessible to molecular cell biologists.
- A network was created using the ANIMO tool, integrating 7 pathways with over 50 nodes and 200 interactions to analyze cell fate decisions and biological scenarios during differentiation.
- The study suggests that a combination of proteins DKK1, FRZB, and GREM1 can help prevent cartilage degeneration by modulating inflammation induced by IL1β in human chondrocytes.
Background: Dysregulation of protein kinase-mediated signaling is an early event in many diseases, including the most common clinical cardiac arrhythmia, atrial fibrillation (AF). Kinomic profiling represents a promising technique to identify candidate kinases.
Objective: In this study we used kinomic profiling to identify kinases altered in AF remodeling using atrial tissue from a canine model of AF (atrial tachypacing).
Background: Computational support is essential in order to reason on the dynamics of biological systems. We have developed the software tool ANIMO (Analysis of Networks with Interactive MOdeling) to provide such computational support and allow insight into the complex networks of signaling events occurring in living cells. ANIMO makes use of timed automata as an underlying model, thereby enabling analysis techniques from computer science like model checking.
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- Massive parallel analysis through array technology is essential for studying genomes and transcriptomes, and similar techniques have been developed for tracking cellular phosphorylation events, known as kinome profiling.
- Despite advancements in bioinformatics for expression arrays, there is a lack of sophisticated analysis tools for kinome profiling, particularly regarding normalization of peptide array data due to the absence of standard "housekeeping" kinases.
- The authors introduce new analysis tools that effectively quantify and normalize peptide array phosphorylation signals, including a method for intraslide gradient correction and a novel interarray normalization procedure called repetitive signal enhancement (RSE), which improves accuracy over traditional methods.