QSAR study of antiplatelet agents

A QSAR methodology that involves multilinear (Hansch-type) and nonlinear (ANN backpropagation) approaches was developed to correlate the antiplatelet activity of 60 benzoxazinone derivatives against factor Xa. The statistical characteristics provided by multilinear model (R2 = 0.821) indicated satisfactory stability and predictive ability, while the ANN predictive ability is somewhat superior (R2 = 0.909). The multilinear model provided insight into the main factors that modulate the inhibitory activity of the investigated compounds.     

HyphArea—Automated analysis of spatiotemporal fungal patterns

In phytopathology quantitative measurements are rarely used to assess crop plant disease symptoms. Instead, a qualitative valuation by eye is often the method of choice. In order to close the gap between subjective human inspection and objective quantitative results, the development of an automated analysis system that is capable of recognizing and characterizing the growth patterns of fungal hyphae in micrograph images was developed. This system should enable the efficient screening of different host-pathogen combinations (e.g., barley—Blumeria graminis, barley—Rhynchosporium secalis) using different microscopy technologies (e.g., bright field, fluorescence). An image segmentation algorithm was developed for gray-scale image data that achieved good results with several microscope imaging protocols. Furthermore, adaptability towards different host-pathogen systems was obtained by using a classification that is based on a genetic algorithm. The developed software system was named HyphArea, since the quantification of the area covered by a hyphal colony is the basic task and prerequisite for all further morphological and statistical analyses in this context. By means of a typical use case the utilization and basic properties of HyphArea could be demonstrated. It was possible to detect statistically significant differences between the growth of an R. secalis wild-type strain and a virulence mutant.     

Biomedical question answering using semantic relations

Background

The proliferation of the scientific literature in the field of biomedicine makes it difficult to keep abreast of current knowledge, even for domain experts. While general Web search engines and specialized information retrieval (IR) systems have made important strides in recent decades, the problem of accurate knowledge extraction from the biomedical literature is far from solved. Classical IR systems usually return a list of documents that have to be read by the user to extract relevant information. This tedious and time-consuming work can be lessened with automatic Question Answering (QA) systems, which aim to provide users with direct and precise answers to their questions. In this work we propose a novel methodology for QA based on semantic relations extracted from the biomedical literature.

Results

We extracted semantic relations with the SemRep natural language processing system from 122,421,765 sentences, which came from 21,014,382 MEDLINE citations (i.e., the complete MEDLINE distribution up to the end of 2012). A total of 58,879,300 semantic relation instances were extracted and organized in a relational database. The QA process is implemented as a search in this database, which is accessed through a Web-based application, called SemBT (available at http://sembt.mf.uni-lj.si). We conducted an extensive evaluation of the proposed methodology in order to estimate the accuracy of extracting a particular semantic relation from a particular sentence. Evaluation was performed by 80 domain experts. In total 7,510 semantic relation instances belonging to 2,675 distinct relations were evaluated 12,083 times. The instances were evaluated as correct 8,228 times (68%).

Conclusions

In this work we propose an innovative methodology for biomedical QA. The system is implemented as a Web-based application that is able to provide precise answers to a wide range of questions. A typical question is answered within a few seconds. The tool has some extensions that make it especially useful for interpretation of DNA microarray results.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0365-3) contains supplementary material, which is available to authorized users.     

Evaluation of Poly(2-Ethyl-2-Oxazoline) Containing Copolymer Networks of Varied Composition as Sustained Metoprolol Tartrate Delivery Systems

Segmented copolymer networks (SCN) based on poly(2-ethyl-2-oxazoline) and containing 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, and/or methyl methacrylate segments have been evaluated as potential sustained release systems of the water soluble cardioselective β-blocker metoprolol tartrate. The structure and properties of the drug carriers were investigated by differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. Swelling kinetics of SCNs in various media was followed, and the conditions for effective MT loading were specified. MT-loaded SCNs with drug content up to 80 wt.% were produced. The release kinetics of metoprolol tartrate from the systems was studied and it was shown that the conetworks of different structure and composition are able to sustain the metoprolol tartrate release without additional excipients.     

Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling

The Eph and Tie cell surface receptors mediate a variety of signaling events during development and in the adult organism. As other receptor tyrosine kinases, they are activated on binding of extracellular ligands and their catalytic activity is tightly regulated on multiple levels. The Eph and Tie receptors display some unique characteristics, including the requirement of ligand-induced receptor clustering for efficient signaling. Interestingly, both Ephs and Ties can mediate different, even opposite, biological effects depending on the specific ligand eliciting the response and on the cellular context. Here we discuss the structural features of these receptors, their interactions with various ligands, as well as functional implications for downstream signaling initiation. The Eph/ephrin structures are already well reviewed and we only provide a brief overview on the initial binding events. We go into more detail discussing the Tie-angiopoietin structures and recognition.     

Charge Movement of a Voltage-Sensitive Fluorescent Protein

The N-terminus of Ciona intestinalis (Ci-VSP) is a voltage-sensing domain (VSD) controlling the activity of a phosphatase domain on the C terminus. By replacing the phosphatase domain with a tandem of fluorescent proteins, CFP and YFP, a family of fluorescence resonance energy transfer-based, genetically encoded voltage-sensing fluorescent protein (VSFP) was created. VSFP2.3, one of the latest versions of this family, showed large changes in YFP emission upon changes in membrane potential with CFP excitation when expressed in Xenopus laevis oocytes. The time course of the fluorescence has two components: the fast component correlates with the time course of sensing current produced by the charge movement, while the slow component is at least one order-of-magnitude slower than the sensing current. This suggests that the tandem of fluorescent proteins reports a secondary conformational transition of the VSD which resembles the relaxation of the VSD of Ci-VSP described in detail for the Ci-VSP. This observation indicates that the relaxation of the VSD of VSFP2.3 is a global conformational change that encompasses the entire S4 segment.     

An integrated approach for the comparative analysis of a multigene family: The nicotianamine synthase genes of barley

Recent genomic projects reveal that about half of the gene repertoire in plant genomes is made up by multigene families. In this paper, a set of structural and phylogenetic analyses have been applied to compare the differently sized nicotianamine synthase (NAS) gene families in barley and rice. Nicotianamine acts as a chelator of iron and other heavy metals and plays a key role in uptake, phloem transport and cytoplasmic distribution of iron, challenging efforts for the breeding of iron-efficient crop plants. Nine barley NAS genes have been mapped, and co-linearity of flanking genes in barley and rice was determined. The combined analyses reveal that the NAS multigene family members in barley originated through at least one duplication event that occurred before the divergence of rice and barley. Additional duplications appear to have occurred within each of the species. Although we detected no evidence for positive selection of recently duplicated genes within species, codon-based tests revealed evidence for positive selection having contributed to the divergence of some amino acids. The integrated comparative and phylogenetic analysis improved our current view of NAS gene family evolution, might facilitate the functional characterization of individual members and is applicable to other multigene families. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Site occupancy and glycan compositional analysis of two soluble recombinant forms of the attachment glycoprotein of Hendra virus

Hendra virus (HeV) continues to cause morbidity and mortality in both humans and horses with a number of sporadic outbreaks. HeV has two structural membrane glycoproteins that mediate the infection of host cells: the attachment (G) and the fusion (F) glycoproteins that are essential for receptor binding and virion-host cell membrane fusion, respectively. N-linked glycosylation of viral envelope proteins are critical post-translation modifications that have been implicated in roles of structural integrity, virus replication and evasion of the host immune response. Deciphering the glycan composition and structure on these glycoproteins may assist in the development of glycan-targeted therapeutic intervention strategies. We examined the site occupancy and glycan composition of recombinant soluble G (sG) glycoproteins expressed in two different mammalian cell systems, transient human embryonic kidney 293 (HEK293) cells and vaccinia virus (VV)-HeLa cells, using a suite of biochemical and biophysical tools: electrophoresis, lectin binding and tandem mass spectrometry. The N-linked glycans of both VV and HEK293-derived sG glycoproteins carried predominantly mono- and disialylated complex-type N-glycans and a smaller population of high mannose-type glycans. All seven consensus sequences for N-linked glycosylation were definitively found to be occupied in the VV-derived protein, whereas only four sites were found and characterized in the HEK293-derived protein. We also report, for the first time, the existence of O-linked glycosylation sites in both proteins. The striking characteristic of both proteins was glycan heterogeneity in both N- and O-linked sites. The structural features of G protein glycosylation were also determined by X-ray crystallography and interactions with the ephrin-B2 receptor are discussed.     

Anammox for ammonia removal from pig manure effluents: Effect of organic matter content on process performance

The anammox process, under different organic loading rates (COD), was evaluated using a semi-continuous UASB reactor at 37 °C. Three different substrates were used: initially, synthetic wastewater, and later, two different pig manure effluents (after UASB-post-digestion and after partial oxidation) diluted with synthetic wastewater. High ammonium removal was achieved, up to 92.1 ± 4.9% for diluted UASB-post-digested effluent (95 mg COD L^?1) and up to 98.5 ± 0.8% for diluted partially oxidized effluent (121 mg COD L^?1). Mass balance clearly showed that an increase in organic loading (from 95 mg COD L^?1 to 237 mg COD L^?1 and from 121 mg COD L^?1 to 290 mg COD L^?1 for the UASB-post-digested effluent and the partially oxidized effluent, respectively) negatively affected the anammox process and facilitated heterotrophic denitrification. Partial oxidation as a pre-treatment method improved ammonium removal at high organic matter concentration. Up to threshold organic load concentration of 142 mg COD L^?1 of UASB-post-digested effluent and 242 mg COD L^?1 of partially oxidized effluent, no effect of organic loading on ammonia removal was registered (ammonium removal was above 80%). However, COD concentrations above 237 mg L^?1 (loading rate of 112 mg COD L^?1 day^?1) for post-digested effluent and above 290 mg L^?1 (loading rate of 136 mg COD L^?1 day^?1) for partially oxidized effluent resulted in complete cease of ammonium removal. Results obtained showed that, denitrification and anammox process were simultaneously occurring in the reactor. Denitrification became the dominant ammonium removal process when the COD loading was increased.