Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum.

Well-characterized small molecules are essential tools for studying the biology and therapeutic relevance of a target protein. However, many compounds reported in the literature and routinely studied in biomedical research lack the potency and selectivity required for mechanistic cellular studies on the function of a given protein. Furthermore, commercially available compounds often do not include useful tools developed by industry as part of their research and development efforts, as they frequently remain proprietary.

Donated chemical probes for open science.

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible.

A simulation study on the activation of cardiac CaMKII delta-isoform and its regulation by phosphatases.

Although the highly conserved Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is known to play an essential role in cardiac myocytes, its involvement in the frequency-dependent acceleration of relaxation is still controversial. To investigate the functional significance of CaMKII autophosphorylation and its regulation by protein phosphatases (PPs) in heart, we developed a new mathematical model for the CaMKIIdelta isoform. Due to better availability of experimental data, the model was first adjusted to the kinetics of the neuronal CaMKIIalpha isoform and then converted to a CaMKIIdelta model by fitting to kinetic data of the delta isoform.

The influence of activation time on contraction force of myocardial tissue: a simulation study.

The efficiency of heart pump function greatly depends on synchronized contraction of myocardial muscle. In this work, contraction simulation of an excitable ventricular tissue cable was constructed to study the influence of excitation patterns on tissue contraction. The tissue cable is composed of elements which contract when excited by an external stimulus.

Mechanism of the Frank-Starling law--a simulation study with a novel cardiac muscle contraction model that includes titin and troponin I.

A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca(2+) sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs).