Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy

The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. To identify the most relevant polymorphisms in human CYPs, a text mining approach was used. We investigated their frequencies in different ethnic groups, the number of drugs that are metabolized by each CYP, the impact of CYP SNPs, as well as CYP expression patterns in different tissues. The most important polymorphic CYPs were found to be 1A2, 2D6, 2C9 and 2C19. Thirty-four common allele variants in Caucasians led to altered enzyme activity. To compare the relevant Caucasian SNPs with those of other ethnicities a search in 1,000 individual genomes was undertaken. We found 199 non-synonymous SNPs with frequencies over one percent in the 1,000 genomes, many of them not described so far. With knowledge of frequent mutations and their impact on CYP activities, it may be possible to predict patient response to certain drugs, as well as adverse side effects. With improved availability of genotyping, our data may provide a resource for an understanding of the effects of specific SNPs in CYPs, enabling the selection of a more personalized treatment regimen

The Transformer database: biotransformation of xenobiotics

As the number of prescribed drugs is constantly rising, drug-drug interactions are an important issue. The simultaneous administration of several drugs can cause severe adverse effects based on interactions with the same metabolizing enzyme(s). The Transformer database (http://bioinformatics.charite.de/transformer) contains integrated information on the three phases of biotransformation (modification, conjugation and excretion) of 3000 drugs and >350 relevant food ingredients (e.g. grapefruit juice) and herbs, which are catalyzed by 400 proteins. A total of 100 000 interactions were found through text mining and manual validation. The 3D structures of 200 relevant proteins are included. The database enables users to search for drugs with a visual display of known interactions with phase I (Cytochrome P450) and phase II enzymes, transporters, food and herbs. For each interaction, PubMed references are given. To detect mutual impairments of drugs, the drug-cocktail tool displays interactions between selected drugs. By choosing the indication for a drug, the tool offers suggestions for alternative medications to avoid metabolic conflicts. Drug interactions can also be visualized in an interactive network view. Additionally, prodrugs, including their mechanisms of activation, and further information on enzymes of biotransformation, including 3D models, can be viewed

Depinning of a superfluid vortex line by Kelvin waves

We measure the interaction of a single superfluid vortex with surface irregularities. While vortex pinning in superconductors usually becomes weaker at higher temperatures, we find the opposite behavior. The pinning steadily increases throughout our measurement range, from 0.15Tc to over 0.5Tc. We also find that moving the other end of the vortex decreases the pinning, so we propose Kelvin waves along the vortex as a depinning mechanism.Comment: 5 figures; substantial revision including 2 new figure

Epitaxial lithium niobate thin films grown by chemical beam epitaxy on sapphire

Lithium Niobate (LiNbO3) is a versatile material with a number of remarkable qualities. It finds application in optical modulators because of its electro-optic properties. Nonlinearity opens its use in bio-physical applications where particles or wires of LiNbO3 can be used as highly localized optical probes. Optical frequency conversion is another possible use, as well. One of the current commercial applications of the material is in optical modulators in telecomunication devices. Nowadays bulk crystals of the material are used. However, in order to make devices more compact and affordable it is necessary to be able to produce LiNbO3 films on suitable substrates with sufficient crystalline and optical quality

DAC-h3: A Proactive Robot Cognitive Architecture to Acquire and Express Knowledge About the World and the Self

This paper introduces a cognitive architecture for a humanoid robot to engage in a proactive, mixed-initiative exploration and manipulation of its environment, where the initiative can originate from both the human and the robot. The framework, based on a biologically-grounded theory of the brain and mind, integrates a reactive interaction engine, a number of state-of-the art perceptual and motor learning algorithms, as well as planning abilities and an autobiographical memory. The architecture as a whole drives the robot behavior to solve the symbol grounding problem, acquire language capabilities, execute goal-oriented behavior, and express a verbal narrative of its own experience in the world. We validate our approach in human-robot interaction experiments with the iCub humanoid robot, showing that the proposed cognitive architecture can be applied in real time within a realistic scenario and that it can be used with naive users

The RNA workbench: best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis. Availability: The RNA workbench is available at https://github.com/bgruening/galaxy-rna-workbench

The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis

Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure