Continuum simulations of acetylcholine diffusion with reaction-determined boundaries in neuromuscular junction models

The reaction-diffusion system of the neuromuscular junction has been modeled in 3D using the finite element package FEtk. The numerical solution of the dynamics of acetylcholine with the detailed reaction processes of acetylcholinesterases and nicotinic acetylcholine receptors has been discussed with the reaction-determined boundary conditions. The simulation results describe the detailed acetylcholine hydrolysis process, and reveal the time-dependent interconversion of the closed and open states of the acetylcholine receptors as well as the percentages of unliganded/monoliganded/diliganded states during the neuro-transmission. The finite element method has demonstrated its flexibility and robustness in modeling large biological systems.     

Divergent effects of peripheral and global neuropeptide Y deletion

Objectives:Neuropeptide Y (NPY) is involved in the coordination of bone mass and adiposity. However, multiple NPY sources exist and their individual contribution to the skeleton and adiposity not known. The objectives of our study were to evaluate the effects of peripheral mesenchymal derived NPY to the skeleton and adiposity and to compare them to the global NPY^KO model.Methods:To study the role of mesenchymal-derived NPY, we crossed conditional NPY (NPY^fl/fl) mice with Prx1cre to generate PrxNPY^KO mice. The bone phenotype was assessed using micro-CT. The skeletal phenotype of PrxNPY^KO mice was subsequently compared to global NPY^KO model. We evaluated body weight, adiposity and functionally assessed the feeding response of NPY neurons to determine whether central NPY signaling was altered by Prx1cre.Results:We identified the increase in cortical parameters in PrxNPY^KO mice with no changes to cancellous bone. This was the opposite phenotype to global NPY^KO mice generated from the same conditional allele. Male NPY^KO mice have increased adiposity, while PrxNPY^KO mice showed no difference, demonstrating that local mesenchymal-derived NPY does not influence adiposity.Conclusion:NPY mediates both positive and negative effects on bone mass via separate regulatory pathways. Deletion of mesenchymal-derived NPY had a positive effect on bone mass.     

Association of octacosanol supplementation with redox status in patients on chronic statin therapy

BackgroundThe uneven lipid-lowering statin effects and statin intolerance raise interest regarding the involvement of coadministration of statins and dietary supplements. This study aimed to evaluate the effects of octacosanol supplementation on markers of redox status in cardiovascular patients on chronic atorvastatin therapy.MethodsA double-blind, randomized, placebo-controlled, single-centre study was conducted. Redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase activity (SOD), total protein sulfhydryl (SHgroups), and paraoxonase 1 (PO N 1) activity] were assessed in 81 patients. According to favorable changes in lipid profile, patients were classified into two groups: responders (n = 35) and non-responders (n = 46), and followed for 13 weeks. A principal component analysis (PCA) was applied to explore the effect of octacosanol supplementation and the relationship between investigated parameters as predictors of responders'' and non-responders'' status.ResultsSignificant decrease in Oxy-score value was found at the endpoint compared to baseline in responders'' group (21.0 (13.4-25.5) versus 15.1 (12.4-18.0); P < 0.01). PCA analysis extracted 4 significant factors in the both groups, whereas extracted factors containing "octacosanol status" variable explained 14.7% and 11.5% of the variance in responders'' and non-responders'' subgroups, respectively.ConclusionsOctacosanol supplementation leads to an improvement of lipid profile and markers of redox status in responders'' group. New studies are needed to validate our results in order to find the best approach for personalized supplementation as a useful adjunct to standard statin therapy.     

Inferring the sources of postglacial range expansion in two large European land snails

Exact locations of glacial refugia are relevant for the study of contemporary biodiversity, not only as places less disturbed during the climatic changes but also as sources of rapid expansion of the biota after the Last Glacial cycle. If continuously inhabited over several of the Quaternary glacial cycles, the refugia are readily identifiable by the accumulated genetic diversity. However, the sources of the Holocene range expansion, particularly important for the emergence of present-day bio- and phylogeographic patterns and for realistic estimation of species’ expansion rates, might have been located at the fringes of the glacial species ranges and lack unique lineages. This problem is pertinent when the variation is explored at slowly evolving genetic markers. We suggest that the location of such source refugia may be approximated by reconstructing the geographic location as a continuous trait evolving along the branches of a phylogenetic tree. We applied this approach, using the BEAST software, on two large southeast European land snail species: Caucasotachea vindobonensis and Helix thessalica. We found evidence for C. vindobonensis refugia in the western Balkans; notable is an apparently old refugium in Bosnia and Herzegovina. The plausible sources of the species’ Holocene range expansion, however, were located around the south-western end of the Carpathians. Although the source areas were likely similar in H. thessalica, some expansion sources suggested by the analyses (e.g., Podolia, Ukraine) appeared implausible and driven by sampling clustered in that area. The applied approach allows for additional exploitation of the mitochondrial data gathered during the past two decades of animal phylogeography studies.     

A new species of the genus <Emphasis Type="Italic">Copidosoma</Emphasis> (Hymenoptera,Chalcidoidea, Encyrtidae) from Israel

A new species of the genus Copidosoma from Israel is described. The female of Copidosoma trjapitzini is similar to those of C. scutellare, C. agrotis, and C. cuproviride. All the four species possess a similar mesosomal sculpture, coarse on the mesoscutum and more or less striate on the scutellum, and the solid clava obliquely truncate at apex. C. trjapitzini differs from C. agrotis in the larger size and from C. cuproviride, in the black head and mesosoma. The type material is deposited in the collection of the Schmalhausen Institute of Zoology (Ukraine, Kiev); two paratypes, at the Zoological Institute, Russian Academy of Sciences (St. Petersburg).     

Spread and population structure of <Emphasis Type=Italic>Cryphonectria parasitica</Emphasis> in a young chestnut orchard in Slovakia

The chestnut blight pathogen Cryphonectria parasitica was studied in a chestnut collection composed of both seedlings and grafts derived from selected Castanea sativa and C. sativa × C. crenata trees located in south-east Slovakia, near village Príbelce on an area of approximately 3.5 ha. The study was conducted during eight years (2003–2010). During this period 133 trees were infected, which represents 59.82% of chestnut trees of all chestnut accessions. Based on the phenotype of the fungus culture and the type of cankers in the field, all isolates were determined to be virulent. No hypovirulent strains were found. No vegetative compatibility (vc) type diversity was observed. More than 130 isolates were analyzed for vc and all were in single vc type, which was identical with EU 12. All isolates assayed for mating type were MAT-1. No perithecia were observed. No significant differences were found between the proportion of cankered and dead cankered trees in seedlings and grafts of hybrid origin (C. sativa × C. crenata) and of C. sativa origin. However, particular seedlings and grafts of hybrid origin seemed to exhibit certain resistance to chestnut blight.     

Temporal and regional changes of superoxide dismutase and glutathione peroxidase activities in rats exposed to focal cerebral ischemia

Reactive oxygen species are important cause of tissue injury during cerebral ischemia and reperfusion (I/R). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are intracellular enzymes responsible for endogenous antioxidant defense of tissues affected by I/R. The aim of this study was to examine temporal and regional changes of SOD and GSH-Px activities in animals exposed to transient focal cerebral ischemia. Male Wistar Hannover rats were subjected to the right middle cerebral artery occlusion for 2?h. The animals were sacrificed immediately, 0·5, 1, 2, 3, 6, 24, 48, 72 or 168?h after ischemic procedure. SOD and GSH-Px activities were determined spectrophotometrically in the hippocampus and parietal cortex, both unilaterally and contralaterally to the occlusion. Sham-operated animals were used as the control group. Our results indicated that transient focal cerebral ischemia causes significant changes in SOD activities in the hippocampus and parietal cortex such as in GSH-Px activities in the parietal cortex, unilaterally and contralaterally to the lesion in rats during different reperfusion periods. Statistically significant activation of GSH-Px was registered neither in the right nor in the left hippocampus of ischemic animals. Copyright ? 2012 John Wiley & Sons, Ltd.     

The WHO network of collaborating centres on standardization and regulatory evaluation of vaccines

WHO Collaborating Centres (CCs) form part of an international collaborative network set up by WHO in support of its mandated programme at the country, intercountry, regional, interregional and global levels, as appropriate. As part of its mandate in the area of biologicals, WHO has broadened the scope of its work and has expanded the range of activities devoted to the establishment of international standards for vaccines. In line with global immunization goals, the need for standards for evaluation of quality, safety and efficacy of new vaccines, as well as those that have been in use for a long time, has significantly increased. Furthermore, complex issues related to new production methodologies, more sophisticated techniques for characterization and laboratory testing, and for nonclinical and clinical evaluation of vaccines have raised a number of regulatory challenges for WHO when requested to assist its Member States. In this context, CCs in the area of standardization of vaccines and biotherapeutics (excluding blood products) have provided technical assistance and have broadened the scope of their work over time. In the area of standardization and regulatory evaluation of vaccines, WHO currently has six CCs as well as one candidate centre for which the designation process has been initiated and a further three candidate centres with great potential. The purpose of the meeting held on 24–26 April 2012 was to improve understanding of WHO's priorities in setting standards, to facilitate their implementation, and to increase transparency of the roles and responsibilities of CCs. The meeting was also an excellent opportunity to explore possibilities for improving collaboration between WHO and CCs, as well as among CCs themselves by working as a CC network. All CCs expressed a wish for increased interaction, information-sharing, collaboration and other ways of working together that may lead to cross-fertilization between the CCs. Synergy was recognized as a significant mechanism for leveraging existing resources in responding to global public health challenges and in addressing WHO's priorities. Agreement was reached for operating as a network of CCs.     

The persistent microbicidal effect in water exposed to the corona discharge

This article describes and particularly explains a new phenomenon of persistent microbicidal effect of water previously exposed to the low-temperature plasma, which cannot be attributed to the acidification only. The direct microbicidal action of plasma is well documented, being mediated by number of reactive particles with a short lifetime. However, we observed the microbicidal effect also in exposed water stored for a month, where it must be mediated by stable particles. In water and in phosphate-buffered saline, the formation of NO_x and corresponding acids, H₂O₂ and O₃ was confirmed after exposition to the low-temperature plasma generated in air by DC negative glow corona and positive streamer discharge. The time course of acidification, H₂O₂ and O₃ formation were deremined. Except uncertain traces of HCN, SIFT-MS analysis of exposed liquids reveals no additional reactive compounds. The microbicidal effect persists almost unchanged during 4 weeks of storage, although O₃ completely and H₂O₂ almost disappears. Staphylococcus epidermidis and Escherichia coli were inactivated within 10 min of incubation in exposed liquids, Candida albicans needs at least 1 h. The solutions prepared by artificial mixing of reactive compounds mimic the action of exposed water, but in lesser extent. The acid milieu is the main cause of the microbicidal effect, but the possibility of still unidentified additional compound remains open.     

Glutamate decarboxylase activity in Trichoderma viride conidia and developing mycelia

Glutamic acid decarboxylase (GAD) activity was measured in homogenates of conidia and both submerged and aerial mycelia of Trichoderma viride. The GAD activity in conidia had a temperature optimum at 30 degrees C and a pH optimum at pH 4. GAD was stimulated by EDTA (2 mM) and was insensitive to treatment with calmodulin antagonists calmidazolium (10 microM) or phenothiazine neuroleptics (60 microM). Cyclosporin A (up to 300 microM) partially inhibited GAD in the homogenate, but not in the supernatant obtained after centrifuging the homogenate. Attempts to release GAD activity from the homogenate using high ionic strength, detergents, or urea failed. Freezing-thawing led to the partial increase of activity in the conidial homogenate. These results indicate that GAD is a membrane-bound enzyme. The highest specific activity of GAD was present in the mitochondrial/vacuolar organellar fraction. Germination of conidia in the submerged culture led to a temporary decrease in GAD activity. After prolonged cultivation, the activity displayed quasi-oscillatory changes. The stationary state was characterized by a high GAD activity. The presence of gamma-aminobutyric acid in the submerged mycelia was demonstrated. In surface culture in the dark, GAD activity increased in a monophasic manner until conidia formation. The illumination of dark-cultivated mycelia by a white-light pulse caused a dramatic increase in GAD activity. Light-induced changes were not observed in mutants with delayed onset of conidiation. In the dark or upon illumination by light pulse, the increase of GAD activity preceded the appearance of conidia. Thus, GAD activity in T. viride is closely associated with its developmental status and may represent a link between differentiation events and energy metabolism.