Expressive rule-based modeling and fast simulation for dynamic compartments.

Compartmentalization is vital for cell biological processes. The field of rule-based stochastic simulation has acknowledged this, and many tools and methods have capabilities for compartmentalization. However, mostly, this is limited to a static compartmental hierarchy and does not integrate compartmental changes.

A-Si/SiO nanolaminates for tuning the complex refractive index and band gap in optical interference coatings.

A- / nanolaminates are deposited by magnetron sputtering and show a decreasing absorption when the a-Si single-layer thickness is reduced from 2.4 to 0.7 .

Implications of different membrane compartmentalization models in particle-based studies.

Studying membrane dynamics is important to understand the cellular response to environmental stimuli. A decisive spatial characteristic of the plasma membrane is its compartmental structure created by the actin-based membrane-skeleton (fences) and anchored transmembrane proteins (pickets). Particle-based reaction-diffusion simulation of the membrane offers a suitable temporal and spatial resolution to analyse its spatially heterogeneous and stochastic dynamics.

Improving optical thickness monitoring by including systematic and process-influenced transmittance deviations.

During optical monitoring using broadband transmittance measurement, the accuracy depends on how both the substrate and the optical path are aligned. We present a correction procedure to improve the accuracy of the monitoring, even if the substrate has features such as absorption or if there is misalignment of the optical path. The substrate in this case can either be a test glass or a product.

An auto-inhibited state of protein kinase G and implications for selective activation.

Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation by cGMP is not well understood.

Dynamical Basis of Allosteric Activation for the Protein Kinase G.

The cGMP-dependent protein kinase (PKG) is required for the progression of the 's life cycle and is therefore a promising malaria drug target. PKG includes four cGMP-binding domains (CBD-A to CBD-D). CBD-D plays a crucial role in PKG regulation as it is the primary determinant for the inhibition and cGMP-dependent activation of the catalytic domain.

Regulation of Cardiac PKA Signaling by cAMP and Oxidants.

Pathologies, such as cancer, inflammatory and cardiac diseases are commonly associated with long-term increased production and release of reactive oxygen species referred to as oxidative stress. Thereby, protein oxidation conveys protein dysfunction and contributes to disease progression. Importantly, trials to scavenge oxidants by systemic antioxidant therapy failed.

Mechanism of allosteric inhibition in the cGMP-dependent protein kinase.

Most malaria deaths are caused by the protozoan parasite Its life cycle is regulated by a cGMP-dependent protein kinase (PKG), whose inhibition is a promising antimalaria strategy. Allosteric kinase inhibitors, such as cGMP analogs, offer enhanced selectivity relative to competitive kinase inhibitors. However, the mechanisms underlying allosteric PKG inhibition are incompletely understood.

Potential based, spatial simulation of dynamically nested particles.

Background: To study cell biological phenomena which depend on diffusion, active transport processes, or the locations of species, modeling and simulation studies need to take space into account. To describe the system as a collection of discrete objects moving and interacting in continuous space, various particle-based reaction diffusion simulators for cell-biological system have been developed. So far the focus has been on particles as solid spheres or points.

New cGMP analogues restrain proliferation and migration of melanoma cells.

Melanoma is one of the most aggressive cancers and displays high resistance to conventional chemotherapy underlining the need for new therapeutic strategies. The cGMP/PKG signaling pathway was detected in melanoma cells and shown to reduce migration, proliferation and to increase apoptosis in different cancer types. In this study, we evaluated the effects on cell viability, cell death, proliferation and migration of novel dimeric cGMP analogues in two melanoma cell lines (MNT1 and SkMel28).

Structural Basis of Analog Specificity in PKG I and II.

Cyclic GMP analogs, 8-Br, 8-pCPT, and PET-cGMP, have been widely used for characterizing cellular functions of cGMP-dependent protein kinase (PKG) I and II isotypes. However, interpreting results obtained using these analogs has been difficult due to their low isotype specificity. Additionally, each isotype has two binding sites with different cGMP affinities and analog selectivities, making understanding the molecular basis for isotype specificity of these compounds even more challenging.