Flavone Derivatives as Inhibitors of Insulin Amyloid-Like Fibril Formation

Several natural and synthetic flavone derivatives have been reported to inhibit formation of amyloid fibrils or to remodel existing fibrils. These studies suggest that the numbers and positions of hydroxyl groups on the flavone rings determine their effectiveness as amyloid inhibitors. In many studies the primary method for determining the effectiveness of inhibition is measuring Thioflavin T (ThT) fluorescence. This method demonstrably results in a number of false positives for inhibition. We studied the effects of 265 commercially available flavone derivatives on insulin fibril formation. We enhanced the effectiveness of ThT fluorescence measurements by fitting kinetic curves to obtain halftime of aggregation (t ₅₀). Maximal values of ThT fluorescence varied two fold or more in one third of all cases, but this did not correlate with changes in t ₅₀. Changes in t ₅₀ values were more accurate measures of inhibition of amyloid formation. We showed that without a change in an assay, but just by observing complete kinetic curves it is possible to eliminate numbers of false positive and sometimes even false negative results. Examining the data from all 265 flavones we confirmed previous observations that identified the importance of hydroxyl groups for inhibition. Our evidence suggests the importance of hydroxyl groups at locations 5, 6, 7, and 4’, and the absence of a hydroxyl group at location 3, for inhibiting amyloid formation. However, the main conclusion is that the positions are not additive. The structures and their effects must be thought of in the context of the whole molecule.     

Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition

Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.     

VoroMQA: Assessment of protein structure quality using interatomic contact areas

In the absence of experimentally determined protein structure many biological questions can be addressed using computational structural models. However, the utility of protein structural models depends on their quality. Therefore, the estimation of the quality of predicted structures is an important problem. One of the approaches to this problem is the use of knowledge‐based statistical potentials. Such methods typically rely on the statistics of distances and angles of residue‐residue or atom‐atom interactions collected from experimentally determined structures. Here, we present VoroMQA (Voronoi tessellation‐based Model Quality Assessment), a new method for the estimation of protein structure quality. Our method combines the idea of statistical potentials with the use of interatomic contact areas instead of distances. Contact areas, derived using Voronoi tessellation of protein structure, are used to describe and seamlessly integrate both explicit interactions between protein atoms and implicit interactions of protein atoms with solvent. VoroMQA produces scores at atomic, residue, and global levels, all in the fixed range from 0 to 1. The method was tested on the CASP data and compared to several other single‐model quality assessment methods. VoroMQA showed strong performance in the recognition of the native structure and in the structural model selection tests, thus demonstrating the efficacy of interatomic contact areas in estimating protein structure quality. The software implementation of VoroMQA is freely available as a standalone application and as a web server at http://bioinformatics.lt/software/voromqa . Proteins 2017; 85:1131–1145. © 2017 Wiley Periodicals, Inc.     

Genetic and allelopathic differences between populations of daisy fleabane Erigeron annuus (L.) Pers. (Asteraceae) from disturbed and stable habitats

The interactions between invasive plants and their habitats may vary at different phases of the invasion process and depend on the phenotypic plasticity or local adaptations of each species. In this study, we investigated whether habitat changes during the invasion process are related to variations in the physiological traits (allelopathic properties) and genetic differentiation of daisy fleabane (Erigeron annuus (L.) Pers.). E. annuus is a winter annual invasive species that originated in North America and is now distributed throughout Europe. Genetic and genotypic diversity analyses were performed for 37 populations of E. annuus based on inter simple sequence repeat (ISSR) polymorphisms. In total, 684 plants were analyzed; 342 were from stable habitats and 342 were from disturbed habitats. The genetic differences among the populations from the different habitats were studied using a Bayesian cluster analysis and an analysis of molecular variance (AMOVA) and by calculating the genetic and genotypic diversity parameters. A germination test using the juglone index was employed to examine the potential allelopathic properties of the plants from the different habitats. Bayesian cluster analysis, AMOVA and allelopathic effects evaluation revealed differences in the allelopathic potential and genetic structure of the E. annuus populations from the disturbed and stable habitats. This differentiation of populations could be associated with founder effects or with different selection pressures among habitats.     

Adaptive habitat preferences in the Tawny Owl Strix aluco

Capsule: Tawny Owls Strix aluco occupying nest boxes preferred habitats which were positively associated with the probability of nesting success.

Aims: We aimed to determine whether or not: (1) Tawny Owls showed habitat preferences when occupying nest boxes; (2) nesting performance was related to the habitats around occupied nest boxes and (3) habitat availability had changed around available and occupied nest boxes between 1995–2004 and 2005–14.

Methods: Tawny Owls were studied using nest boxes erected in a commercial forest. During nest boxes checks (724 cases), data on occupancy and nesting performance (88 cases) were recorded, and habitat within a 0.4?km radius around nest boxes was analysed.

Results: Tawny Owls had preferences for clearings within forests, mature forests and grasslands but avoided young forests. We found a positive relationship between nesting success and abundance of clearings within the forest, and a negative relationship between nesting success and abundance of young forests. A change in habitat preferences over the two decades was evident, but habitat availabilities remained similar.

Conclusions: Findings indicate adaptive habitat selection in Tawny Owls because preferred habitats were associated with higher fitness and this type of habitat became more frequently selected over time.     

Description of Crenosoma vismani n. sp., parasitic in the lungs of Lynx lynx (L.) (Carnivora: Felidae), with identification key to the species of the genus Crenosoma Molin, 1861 (Nematoda: Crenosomatidae)

A new species of Crenosoma Molin, 1861 is described from the lungs of the Eurasian lynx, Lynx lynx (L.) (Carnivora: Felidae). Crenosoma vismani n. sp. differs from other species of the genus in the morphology of the male copulatory organs (two ventral rays originating from a common stem; three lateral rays with common stem; gubernaculum 79–92 μm long, well developed, spoon-shaped; spicules 232–253 μm long, slightly curved, with robust dorsal appendage) and a vulva with rounded, prominent vulvar cuticular appendage is located in middle region of body in females. An analysis of the morphology and life-cycle data for Crenosoma petrowi Morozov, 1939 from Ursus americanus Pallas indicate that this nematode should be described as a new species. The validity of Crenosoma schulzi Gagarin, 1958 is resurrected. A new identification key for the species of Crenosoma is provided. Published records of the genus Crenosoma from definitive hosts and patterns of host specificity are presented. Morphological data revealed that the genus Crenosoma should contain 15 species (14 with valid names) with different host specificity, ranging from oioxenous to euryxenous. However, a review of the current genetic data indicates that the actual number of Crenosoma spp. is greater, and the host range is still unknown, even in Europe.

     

Specific and non-specific cestodes of shrews (Eulipotyphla: Soricidae) in Europe with a description of Coronacanthus longicirrosus n. sp (Cestoda: Hymenolepididae)

Systematic Parasitology - This paper presents a review of host specificity among cestodes collected from Soricidae mammals in Europe and a revision of cestodes preserved in formalin in the...     

Development of new analytical systems based on biocatalysers

A new amperometric analytical system based on biocatalysers is described. The study examined the use of immobilized multienzyme systems, sensitivity increase of devices by chemical amplification, the use of dehydrogenases, hydrolases and microorganisms and the application of biochemical cells as analytical devices. The macrokinetic dependence of the action of systems is considered and the means of their possible development are proposed.