Berichtigung zu Heft 16/1

Ohne Zusammenfassung The online version of the original article can be found under doi:.     

ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration.     

Mechanistic and molecular investigations on stabilization of horseradish peroxidase C

The enzyme horseradish peroxidase (HRP) shows a decreasing activity when the enzyme's substrate hydrogen peroxide is present with the degree of inactivation being dependent on the incubation time and the hydrogen peroxide concentration. Incubation times of some minutes do not inactivate the enzyme independent of the H2O2 concentration. After several hours, only 50% of the activity is found for a medium H2O2 excess, and a >100-fold excess of H2O2 completely inactivates the enzyme. Polymeric additives, in particular Gafquat, lead to higher residual activities, whereas stabilizers, such as aminopyrine, preserve the full activity. Circular dichroism (CD) measurements reveal that the enzyme structure remains more or less unchanged when hydrogen peroxide is added. Only when a 1000-fold excess of hydrogen peroxide is present are structural changes observed. UV spectra highlight that the heme group in the enzyme is affected by hydrogen peroxide in a first step. Without any prolonged incubation, a decrease of the Soret band to approximately 50% is found for low hydrogen peroxide concentrations (HRP/H2O2 from 1:1 to 1:100). Higher H2O2 concentrations lead to the formation of catalytically inactive HRP forms. Preincubation of Gafquat, which is a copolymer from vinylpyrrolidone and derivatized methyl methacrylate, with hydrogen peroxide shifts the influence of hydrogen peroxide to higher concentrations, the shift being dependent on the Gafquat concentration. This effect is not observed for other polymers, such as dextrans, but it is also found for the stabilizer aminopyrine. Extended incubation times (24 h) of HRP together with H2O2, however, lead to an at least partial recovery of the Soret band for lower H2O2 concentrations (H2O2/HRP from 1:1 to 1:100). When hydrogen peroxide is used in a >100 fold excess, the heme group is irreversibly destroyed, and even the characteristic band of cpd III is not found. Here, the presence of Gafquat only reduces the degree of destruction. Computer modeling of the interaction between the polymers and the enzyme shows no specific binding sites for the functional groups of the vinylpyrrolidone-methacrylate copolymer Gafquat or of DEAE-dextran on the enzyme, whereas for the only activating polymer, polyethylenimine clustering of binding sites is observed.     

A highly sensitive NO2-selective optode membrane

A new NO₂-sensitive polymeric optode membrane is introduced. It takes advantage of the reactivity of NO₂ with an aquacyanocobalt(III)-cobyrinate derivative. The detection mechanism leads to a protonation of the Nile Blue derivative ETH 5418, which changes its visible spectrum thereby. The polymer layer also contains the aquacyanocobalt(III)-cobyrinate derivative, which significantly reduces the response time and improves the operational lifetime of the sensor compared to a blank membrane. No cross-sensitivity to NO, CO, CO₂ and only a small interference by SO₂ was observed.

A large variety of polymers and plasticizers were tested in order to achieve resistance to high temperature and to improve the lifetime of the sensor. Until now, the plasticized poly(vinylchloride) membranes still remain the material of choice in view of a good compromise between stability, response time and solubility of components.     

Model-based pairwise testing for feature interaction coverage in software product line engineering

Testing software product lines (SPLs) is very challenging due to a high degree of variability leading to an enormous number of possible products. The vast majority of today??s testing approaches for SPLs validate products individually using different kinds of reuse techniques for testing. Because of their reusability and adaptability capabilities, model-based approaches are suitable to describe variability and are therefore frequently used for implementation and testing purposes of SPLs. Due to the enormous number of possible products, individual product testing becomes more and more infeasible. Pairwise testing offers one possibility to test a subset of all possible products. However, according to the best of our knowledge, there is no contribution discussing and rating this approach in the SPL context. In this contribution, we provide a mapping between feature models describing the common and variable parts of an SPL and a reusable test model in the form of statecharts. Thereby, we interrelate feature model-based coverage criteria and test model-based coverage criteria such as control and data flow coverage and are therefore able to discuss the potentials and limitations of pairwise testing. We pay particular attention to test requirements for feature interactions constituting a major challenge in SPL engineering. We give a concise definition of feature dependencies and feature interactions from a testing point of view, and we discuss adequacy criteria for SPL coverage under pairwise feature interaction testing and give a generalization to the T-wise case. The concept and implementation of our approach are evaluated by means of a case study from the automotive domain.     

Synthesis of molecular sieves from Chilean kaolinites: 1. Synthesis of NaA type zeolites

The synthesis of NaA type zeolites has been studied at autogenous pressure using Chilean kaolins as starting materials. The ratios of SiO₂/Al₂O₃, Na₂O/SiO₂, H₂O/Na₂O have been set at 1.9 or 2.5, 0.6 or 1.0 and 50 or 90, respectively. Reaction times have been 5 or 15 h and reaction temperature 80 or 100°C. The influence of these parameters on the textural and structural properties of the zeolite has been studied. All samples have been characterized by X‐ray diffraction, infrared spectroscopy, scanning electron microscopy, differential thermal analysis and cation exchange capacity. The best conditions for synthesis are: SiO₂/Al₂O₃=2.5, Na₂O/SiO₂=1.0, H₂O/Na₂O=50 and 15 h reaction time at 100°C. © 1999 Society of Chemical Industry     

Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex

The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.     

Fusion of Mitochondria to 3-D Networks,Autophagy and Increased Organelle Contacts are Important Subcellular Hallmarks during Cold Stress in Plants

Low temperature stress has a severe impact on the distribution, physiology, and survival of plants in their natural habitats. While numerous studies have focused on the physiological and molecular adjustments to low temperatures, this study provides evidence that cold induced physiological responses coincide with distinct ultrastructural alterations. Three plants from different evolutionary levels and habitats were investigated: The freshwater alga Micrasterias denticulata, the aquatic plant Lemna sp., and the nival plant Ranunculus glacialis. Ultrastructural alterations during low temperature stress were determined by the employment of 2-D transmission electron microscopy and 3-D reconstructions from focused ion beam–scanning electron microscopic series. With decreasing temperatures, increasing numbers of organelle contacts and particularly the fusion of mitochondria to 3-dimensional networks were observed. We assume that the increase or at least maintenance of respiration during low temperature stress is likely to be based on these mitochondrial interconnections. Moreover, it is shown that autophagy and degeneration processes accompany freezing stress in Lemna and R. glacialis. This might be an essential mechanism to recycle damaged cytoplasmic constituents to maintain the cellular metabolism during freezing stress.