A Brief Introduction to Current Cancer Gene Therapy.

Gene therapy has started in the late 1980s as novel, clinically applicable therapeutic option. It revolutionized the treatment of genetic diseases with the initial intent to repair or replace defective genes. Gene therapy has been adapted for treatment of malignant diseases to improve the outcome of cancer patients.

Dynamic publication media with the COPASI R Connector (CoRC).

In this article we show how dynamic publication media and the COPASI R Connector (CoRC) can be combined in a natural and synergistic way to communicate (biochemical) models. Dynamic publication media are becoming a popular tool for authors to effectively compose and publish their work. They are built from templates and the final documents are created dynamically.

CoRC: the COPASI R Connector.

Motivation: COPASI is a biochemical simulator and model analyzer which has found widespread use in academic research, teaching and beyond. One of COPASI's strengths is its graphical user interface, and this is what most users work with. COPASI also provides a command-line tool.

Long-term apical bone gain after implant placement combined with internal sinus-floor elevation without graft.

Background: To assess changes in apical bone height/bone gain over up to 8 years after implant placement combined with simultaneous internal sinus-floor elevation (ISFE) without use of graft.

Methods: 217 implants were placed in combination with graft-free ISFE and successfully healed in the posterior maxilla of 138 patients. Radiographs after surgery across an evaluation time of up to 8 years were analyzed.

Selective Inactivation of Reelin in Inhibitory Interneurons Leads to Subtle Changes in the Dentate Gyrus But Leaves Cortical Layering and Behavior Unaffected.

Reelin is an extracellular matrix protein, known for its dual role in neuronal migration during brain development and in synaptic plasticity at adult stages. During the perinatal phase, Reelin expression switches from Cajal-Retzius (CR) cells, its main source before birth, to inhibitory interneurons (IN), the main source of Reelin in the adult forebrain. IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear.

Data Management in Computational Systems Biology: Exploring Standards, Tools, Databases, and Packaging Best Practices.

Computational systems biology involves integrating heterogeneous datasets in order to generate models. These models can assist with understanding and prediction of biological phenomena. Generating datasets and integrating them into models involves a wide range of scientific expertise.

Requirements for band-pass activation of Ca-sensitive proteins such as NFAT.

Several proteins are sensitive to frequency-modulated oscillations of calcium levels. Most of them exhibit increased activities for faster frequencies, a characteristic here referred to as high-pass activation. In contrast, the transcription factor NFAT is optimally activated at a specific frequency, a behaviour we call band-pass activation.

COPASI and its applications in biotechnology.

COPASI is software used for the creation, modification, simulation and computational analysis of kinetic models in various fields. It is open-source, available for all major platforms and provides a user-friendly graphical user interface, but is also controllable via the command line and scripting languages. These are likely reasons for its wide acceptance.

Vectors and strategies for nonviral cancer gene therapy.

Introduction: This review presents recent developments in the use of nonviral vectors and transfer technologies in cancer gene therapy. Tremendous progress has been made in developing cancer gene therapy in ways that could be applicable to treatments. Numerous efforts are focused on methods of attacking known and novel targets more efficiently and specifically.

Exploiting intrinsic fluctuations to identify model parameters.

Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships.

PKC-mediated inhibitory feedback of the cholecystokinin 1 receptor controls the shape of oscillatory Ca²⁺ signals.

Translation of extracellular hormonal input into cellular responses is often mediated by repetitive increases in cytosolic free Ca(2+) concentration ([Ca(2+) ]c ). Amplitude, duration and frequency of these so-called [Ca(2+) ]c oscillations then carry information about the nature and concentration of the extracellular signalling molecule. At present, there are different hypotheses concerning the induction and control of these oscillations.

Zinc depletion regulates the processing and secretion of IL-1β.

Sterile inflammation contributes to many common and serious human diseases. The pro-inflammatory cytokine interleukin-1β (IL-1β) drives sterile inflammatory responses and is thus a very attractive therapeutic target. Activation of IL-1β in sterile diseases commonly requires an intracellular multi-protein complex called the NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome.

Role of the postnatal radial glial scaffold for the development of the dentate gyrus as revealed by Reelin signaling mutant mice.

During dentate gyrus development, the early embryonic radial glial scaffold is replaced by a secondary glial scaffold around birth. In contrast to neocortical and early dentate gyrus radial glial cells, these postnatal glial cells are severely altered with regard to position and morphology in reeler mice lacking the secreted protein Reelin. In this study, we focus on the functional impact of these defects.

An in vivo control map for the eukaryotic mRNA translation machinery.

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control.

Biochemical fluctuations, optimisation and the linear noise approximation.

Background: Stochastic fluctuations in molecular numbers have been in many cases shown to be crucial for the understanding of biochemical systems. However, the systematic study of these fluctuations is severely hindered by the high computational demand of stochastic simulation algorithms. This is particularly problematic when, as is often the case, some or many model parameters are not well known.

Efficient discovery of anti-inflammatory small-molecule combinations using evolutionary computing.

The control of biochemical fluxes is distributed, and to perturb complex intracellular networks effectively it is often necessary to modulate several steps simultaneously. However, the number of possible permutations leads to a combinatorial explosion in the number of experiments that would have to be performed in a complete analysis. We used a multiobjective evolutionary algorithm to optimize reagent combinations from a dynamic chemical library of 33 compounds with established or predicted targets in the regulatory network controlling IL-1β expression.

Biochemical simulations: stochastic, approximate stochastic and hybrid approaches.

Computer simulations have become an invaluable tool to study the sometimes counterintuitive temporal dynamics of (bio-)chemical systems. In particular, stochastic simulation methods have attracted increasing interest recently. In contrast to the well-known deterministic approach based on ordinary differential equations, they can capture effects that occur due to the underlying discreteness of the systems and random fluctuations in molecular numbers.

Information transfer in signaling pathways: a study using coupled simulated and experimental data.

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.

COPASI--a COmplex PAthway SImulator.

Motivation: Simulation and modeling is becoming a standard approach to understand complex biochemical processes. Therefore, there is a big need for software tools that allow access to diverse simulation and modeling methods as well as support for the usage of these methods.

Results: Here, we present COPASI, a platform-independent and user-friendly biochemical simulator that offers several unique features.

Transition from stochastic to deterministic behavior in calcium oscillations.

Simulation and modeling is becoming more and more important when studying complex biochemical systems. Most often, ordinary differential equations are employed for this purpose. However, these are only applicable when the numbers of participating molecules in the biochemical systems are large enough to be treated as concentrations.