Evaluation of the Role of Glutathione in the Lead-Induced Toxicity in Saccharomyces cerevisiae

A Gram-negative, aerobic, short-rod-shaped, non-motile bacterium designated Rs7^T, was isolated from peat soil collected from Russia and was characterized to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that the strain Rs7^T belongs to the class Betaproteobacteria. The highest degree of sequence similarities were determined to be with Burkholderia tropica Ppe8^T (98.4 %), Burkholderia unamae MTI-641^T (97.8 %), Burkholderia bannensis E25^T (97.7 %), Burkholderia heleia SA41^T (97.0 %), and Burkholderia sacchari IPT101^T (97.0 %). Chemotaxonomic data revealed that the strain Rs7^T possesses ubiquinone Q-8. The polar lipid profile of strain Rs7^T contained phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and an unknown amino phospholipid. The predominant fatty acids were C_16:0, C_19:0 cyclo ω8c, and C_17:0 cyclo, all of which corroborated the assignment of the strain to the genus Burkholderia. The DNA G+C content was 63.2 mol%. DNA–DNA hybridization experiments showed less than 37.8 % DNA relatedness with closely related type strains, thus confirming separate species status. The results of physiological and biochemical tests allowed phenotypic differentiation of strain Rs7^T from the members of the genus Burkholderia. Based on these data, Rs7^T (=KEMC 7302-068^T = JCM 18069^T) should be classified as the type strain for a novel Burkholderia species, for which the name Burkholderia humi sp. nov. is proposed.     

Two- Versus Three-Dimensional Morphometric Approaches in Macroevolution: Insight from the Mandible of Caviomorph Rodents

Morphological variation is one of the most studied dimensions of evolutionary biology, given its close relationship with the ecological aspects of biological diversification. In this work we examine the differences between the use of two- and three-dimensional morphometric techniques for the analysis of macroevolutionary patterns of morphological variation in the mandible of the South American caviomorph rodents, which displays varying degrees of hystricognathy. The variation patterns were similar for 2D and 3D coordinate datasets. However, phylogenetic comparative statistical analyses showed widely different results for mandible variation. Both the phylogenetic signal values and the results of phylogenetic regressions were markedly different between the two macroevolutionary mandible datasets. This suggests that the inclusion of the third coordinate to characterize a hystricognathous mandible may lead to completely different interpretations concerning the processes that could be regulating the morphological diversification of the caviomorph mandible. We also compare these results with the 2D and 3D macroevolutionary patterns of variation in cranial shape and the intra-specific mandible variation. The variation patterns were similar for 2D and 3D coordinate for all these comparative datasets. The differing results obtained at different evolutionary scales, give strength to the statement about careful selection of data not only in studies of morphological variation in caviomorphs but also for other groups of organisms.     

Complexes of Trypanosoma cruzi Sterol 14α-Demethylase (CYP51) with Two Pyridine-based Drug Candidates for Chagas Disease: STRUCTURAL BASIS FOR PATHOGEN SELECTIVITY*

Chagas disease, caused by the eukaryotic (protozoan) parasite Trypanosoma cruzi, is an alarming emerging global health problem with no clinical drugs available to treat the chronic stage. Azole inhibitors of sterol 14α-demethylase (CYP51) were proven effective against Chagas, and antifungal drugs posaconazole and ravuconazole have entered clinical trials in Spain, Bolivia, and Argentina. Here we present the x-ray structures of T. cruzi CYP51 in complexes with two alternative drug candidates, pyridine derivatives (S)-(4-chlorophenyl)-1-(4-(4-(trifluoromethyl)phenyl)-piperazin-1-yl)-2-(pyridin-3-yl)ethanone (UDO; Protein Data Bank code 3ZG2) and N-[4-(trifluoromethyl)phenyl]-N-[1-[5-(trifluoromethyl)-2-pyridyl]-4-piperi-dyl]pyridin-3-amine (UDD; Protein Data Bank code 3ZG3). These compounds have been developed by the Drugs for Neglected Diseases initiative (DNDi) and are highly promising antichagasic agents in both cellular and in vivo experiments. The binding parameters and inhibitory effects on sterol 14α-demethylase activity in reconstituted enzyme reactions confirmed UDO and UDD as potent and selective T. cruzi CYP51 inhibitors. Comparative analysis of the pyridine- and azole-bound CYP51 structures uncovered the features that make UDO and UDD T. cruzi CYP51-specific. The structures suggest that although a precise fit between the shape of the inhibitor molecules and T. cruzi CYP51 active site topology underlies their high inhibitory potency, a longer coordination bond between the catalytic heme iron and the pyridine nitrogen implies a weaker influence of pyridines on the iron reduction potential, which may be the basis for the observed selectivity of these compounds toward the target enzyme versus other cytochrome P450s, including human drug-metabolizing P450s. These findings may pave the way for the development of novel CYP51-targeted drugs with optimized metabolic properties that are very much needed for the treatment of human infections caused by eukaryotic microbial pathogens.     

Neuromuscular response to varying pressures created by tightness of restriction cuff

Variation in regional body composition between genders may change the degree of pressure created by the tightness of cuff used during blood flow restriction training resulting in changes in the level of neuromuscular activation. This study investigates the effects of tightness of cuff and skin and subcutaneous fat thickness on electromyography (EMG) amplitude (RMS) and median frequency (MDF) during exercises and strength testing. Subjects performed knee-extension exercises with varying tightness of cuff while using EMG to measure changes in neuromuscular response. EMG RMS was significantly affected by tightness of cuff and skin and subcutaneous fat thickness. The strongest individual variable for the changes in MDF was also skin and subcutaneous-fat thickness. The changes in EMG response due to tightness of cuff and the effect of skin and subcutaneous fat thickness on tightness of cuff prove the importance of details on BFR protocol and leg composition on neuromuscular function during BFR exercises.     

Isolation and characterization of microsatellites in Aphidius ervi (Hymenoptera: Braconidae) and their applicability to related species

Aphidius ervi (Hymenoptera: Braconidae) is an important biological control agent of aphids, and a model organism for the study of host–parasitoid ecology and evolution. We isolated microsatellite loci from A. ervi to examine the genetic effects of its introduction from Europe to North America. We present primers for 11 microsatellites from A. ervi. We have assayed six of these loci for variability and found from two to 37 alleles. These six primer pairs were tested on 17 related species and appear broadly applicable. These microsatellite loci provide a new tool for research on A. ervi and its relatives.     

Colocalization of (3H)-adenosine accumulation and GABA immunoreactivity in the chicken and rabbit retinas

Using combined autoradiography and immunohistochemistry, we have compared (3H)-adenosine accumulation and GABA immunoreactivity in the chicken and rabbit retinas. Colocalization of the two markers was observed in a subset of amacrine cells and in certain cell bodies in the ganglion cell layer in both species and in a few horizontal cells in the chicken retina. Cells that contained only (3H)-adenosine or GABA were also seen. The degree of colocalization differed greatly between the two species. The results demonstrate a morphological relationship between the adenosine and GABA systems and provides information on the possible anatomical substrates underlying at least some types of functional interactions.     

Oestradiol changes the dielectric structure of bilayer membranes

The addition of the hormone Oestradiol to Phosphatidylcholine-Cholesterol membrane changes the frequency dependence of the membrane impedance. It increases severalfold the electrical admittance of the polar regions and consequently provides a conducting shunt from the hydrocarbon region to the aqueous phase.