Protecting isolated reptile populations outside their main area of distribution: a predictive model of the Dice snake, Natrixtessellata, distribution in the Czech Republic.

Marginal populations of animals are highly susceptible to environmental pressures associated with climatic changes. Understanding their distribution and ecological requirements is, thus, essential for the development of efficient conservation strategies. The dice snake, Natrixtessellata, is listed as critically endangered in the Czech Republic. In certain regions (Bohemia and Silesia), its populations are located beyond the northern border of the continuous range of the species, while the south Moravian populations are connected to it. Based on the statewide database of the Czech Nature Conservation Agency, we created a predictive model and determined key factors influencing the species distribution. The most relevant factors were: watercourses and bodies, average annual temperatures, altitude, slope inclination and precipitation seasonality. The model fits the presence records well and is applicable in both theory and practice of the species conservation - for example, focusing faunistic research to certain areas, critical analysis of controversial presence reports and as an input for species management in the form of repatriation and introduction.

Species-specific habitat preferences do not shape the structure of a crested newt hybrid zone (Triturus cristatus x T. carnifex).

Reproductive isolation barriers maintain the integrity of species by preventing interspecific gene flow. They involve temporal, habitat or behavioral isolation acting before fertilization, and postzygotic isolation manifested as hybrid mortality or sterility. One of the approaches of how to study reproductive isolation barriers is through the analysis of hybrid zones. In this paper, we describe the structure of a hybrid zone between two crested newt species (Triturus cristatus and T. carnifex) in the southern part of the Czech Republic using morphological, microsatellite, and mitochondrial (mtDNA) markers. Specifically, we tested the hypothesis that the structure of the hybrid zone is maintained by species-specific habitat preferences. Comparing the genetic structure of populations with geographical and ecological parameters, we found that the hybrid zone was structured primarily geographically, with T. cristatus-like populations occurring in the northeast and T. carnifex-like populations in the southwest. Despite T. cristatus tending to occur in deeper ponds and T. carnifex on localities with more shading, the effect of both ecological parameters on the structure of the zone was minimal. Next, we corroborated that T. carnifex individuals and some hybrids possess mtDNA of T. dobrogicus, whose nuclear background was not detected in the studied hybrid zone. Hybridization between T. carnifex and T. dobrogicus (resulting in unidirectional mtDNA introgression) had to predate subsequent formation of the hybrid zone between T. cristatus and T. carnifex. Populations of crested newts in the southern part of the Czech Republic thus represent a genetic mosaic of nuclear and mitochondrial genomes of three species.

Inhibition of human drug metabolizing cytochrome P450 enzymes by plant isoquinoline alkaloids.

The human cytochrome P450 (CYP) enzymes play a major role in the metabolism of endobiotics and numerous xenobiotics including drugs. Therefore it is the standard procedure to test new drug candidates for interactions with CYP enzymes during the preclinical development phase. The purpose of this study was to determine in vitro CYP inhibition potencies of a set of isoquinoline alkaloids to gain insight into interactions of novel chemical structures with CYP enzymes. These alkaloids (n=36) consist of compounds isolated from the Papaveraceae family (n=20), synthetic analogs (n=15), and one commercial compound. Their inhibitory activity was determined towards all principal human drug metabolizing CYP enzymes: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4. All alkaloids were assayed in vitro in a 96-well plate format using pro-fluorescent probe substrates and recombinant human CYP enzymes. Many of these alkaloids inhibited the CYP3A4 form, with 30/36 alkaloids inhibiting CYP3A4 with at least moderate potency (IC50 < 10 µM) and 15/36 inhibiting CYP3A4 potently (IC50 < 1 µM). Among them corydine, parfumine and 8-methyl-2,3,10,11-tetraethoxyberbine were potent and selective inhibitors for CYP3A4. CYP2D6 was inhibited with at least moderate potency by 26/34 alkaloids. CYP2C19 was inhibited by 15/36 alkaloids at least moderate potently, whereas CYP1A2, CYP2B6, CYP2C8, and CYP2C9 were inhibited to a lesser degree. CYP2A6 was not significantly inhibited by any of the alkaloids. The results provide initial structure-activity information about the interaction of isoquinoline alkaloids with major human xenobiotic-metabolizing CYP enzymes, and illustrate potential novel structures as CYP form-selective inhibitors.

Volumetric modeling and interactive cutting of deformable bodies.

A new approach for the interactive simulation of viscoelastic object cutting is presented. Two synchronized geometrical models at different resolutions are used, both derived from medical images. In contrast with most previous approaches, the blade deforms the object, and cutting occurs once a contact pressure threshold is exceeded. Moreover, we achieve interactive simulation rates by embedding a high-resolution geometry within a regular grid with arbitrary resolution. This allows to trade off accuracy for speed in the computation of deformations. The input data is a high-resolution volumetric model of the objects. The surface model of the object, used for rendering as well as collision detection and response, is a polygonal level set of the volumetric data. It is embedded in the volume model using barycentric coordinates. Cutting is performed by removing voxels at the fine level, and updating the surface and volume models accordingly. We introduce a new data structure, which we call a Dynamic Branched Grid, in order to preserve the fine-level topology at the coarse level. When an element of the coarse volumetric model is cut, it is replaced by a number of superimposed elements with the same size and at the same rest position as the original one. Each new element is assigned a part of material contained in the original one, and the mass and stiffness are recomputed accordingly. The well-known problem of creating small, ill-shaped finite elements while remeshing is thus completely avoided.

Stable cutting of deformable objects in virtual environments using XFEM.

Most deformable object simulators suffer from stability problems caused by material slivers in the cut vicinity. The extended finite element method (XFEM) is a novel approach that uses element enrichment to effectively model discontinuities. In combination with an appropriate mass-lumping technique, XFEM provides a stable simulation regardless of cut location.

A stable cutting method for finite elements based virtual surgery simulation.

In this paper we present a novel approach for stable interactive cutting of deformable objects in virtual environments. Our method is based on the extended finite elements method, allowing for a modeling of discontinuities without remeshing. As no new elements are created, the impact on simulation performance is minimized. We also propose an appropriate mass lumping technique to guarantee for the stability of the simulation regardless of the position of the cut.

Adaptive soft tissue deformation for a virtual reality surgical trainer.

Real time tissue deformation is an important aspect of interactive virtual reality (VR) environments such as medical trainers. Most approaches in deformable modelling use a fixed space discretization. A surgical trainer requires high plausibility of the deformations especially in the area close to the instrument. As the area of intervention is not known a priori, adaptive techniques have to be applied. We present an approach for real time deformation of soft tissue based on a regular FEM mesh of cube elements as opposed to a mesh of tetrahedral elements used by the majority of soft tissue simulators. A regular mesh structure simplifies the local refinement operation as the elements topology and stiffness are known implicitly. We propose an octree-based adaptive multiresolution extension of our basic approach. The volumetric representation of the deformed object is created automatically from medical images or by voxelization of a surface model. The resolution of the volumetric representation is independent of the surface geometry resolution. The surface is deformed according to the simulation performed on the underlying volumetric mesh.