Echocardiographic quantification of myocardial function using tissue deformation imaging, a guide to image acquisition and analysis using tissue Doppler and speckle tracking

Recent developments in the field of echocardiography have allowed the cardiologist to objectively quantify regional and global myocardial function. Regional deformation (strain) and deformation rate (strain-rate) can be calculated non-invasively in both the left and right ventricle, providing information on regional (dys-)function in a variety of clinical settings. Although this promising novel technique is increasingly applied in clinical and preclinical research, knowledge about the principles, limitations and technical issues of this technique is mandatory for reliable results and for implementation both in the clinical as well as the scientific field. In this article, we aim to explain the fundamental concepts and potential clinical applicability of strain and strain-rate for both tissue Doppler imaging (TDI) derived and speckle tracking (2D-strain) derived deformation imaging. In addition, a step-by-step approach to image acquisition and post processing is proposed. Finally, clinical examples of deformation imaging in hypertrophic cardiomyopathy (HCM), cardiac resynchronization therapy (CRT) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are presented.     

Phylogeny of Palaearctic wheatears (genus Oenanthe)--congruence between morphometric and molecular data

Wheatears of the genus Oenanthe are birds specialized to desert ecosystems in the Palaearctic region from Morocco to China. Although they have been the subject of many morphological and ecological studies, no molecular data have been used to elucidate their phylogenetic relationships, and, their relationships are still debated. Here we use DNA sequences of 1180 bp of two mitochondrial genes, 16S rRNA and cytochrome oxidase subunit I, from 32 individuals from Middle East and North Africa, and Bayesian methods to derive a phylogeny for 11 species of Oenanthe. The resulting tree supported three major clades: (A) O. alboniger, O. chrysopygia, O. lugens, O. finschii, O. leucopyga, O. picata, O. moesta, (B) O. deserti and O. pleschanka; and (C) O. isabellina and O. oenanthe. These results largely differ from previous hypotheses based on analysis of morphological and chromatic characters. However, the two clades (B) and (C) were also supported by a phenetic analysis of new morphometric data presented here, indicating that characters related to colouration and ecology in Oenanthe are more strongly influenced by homoplasy than those of body shape.     

Health risk assessment of fluoride in water distribution network of Mashhad,Iran

High and low levels of fluoride in drinking waters have been considered as a major public health issue in recent years. This cross-sectional study was conducted over five consecutive years (from 2012 to 2016) in the water distribution network of Mashhad city, Iran with the objectives of determining levels of fluoride and to perform health risk assessment among residents in the study area. Water samples were taken from 30 stations and were analyzed using UV-visible spectrophotometer. The mean annual concentrations of fluoride in all stations during five years of consecutive study were lower than the respective maximum permissible limits (1.5 mg/L) in water as regulated by the WHO. The human health risk assessment was performed by calculating the chronic daily intake and hazard quotient (HQ) of fluoride through human oral intake for adults (men and women) and children for each year during a five-year study. Health risk analysis in this study presented that the non-carcinogenic risk associated with fluoride exposure through drinking water in Mashhad was mostly acceptable because the mean HQ values of fluoride were lower than 1.     

Isocostic Acid,a Promising Bioactive Agent from the Essential Oil of Inula viscosa (L.): Insights from Drug Likeness Properties,Molecular Docking and SAR Analysis

The chemical composition of the essential oil (LEO) and its volatile fractions (V₁–V₁₀) collected during the hydrodistillation process every 15 min from the fresh leaves of I. viscosa (L.), growing in Tunisia, were analyzed by GC‐FID and GC/MS. Eighty‐two compounds, representing 90.9–99.4 % of the total samples, were identified. The crude essential oil (LEO) and its fractions (V₁–V₁₀) were characterized by the presence of a high amount of oxygenated sesquiterpenes (82.7–95.8 %). Isocostic acid ( 1 ) was found to be the most abundant component (37.4–83.9 %) and was isolated from the same essential oil over silica gel column chromatography and identified by spectroscopic methods (¹H, ¹³C, DEPT 135 NMR and EI‐MS) and by comparison with literature data. Furthermore, the fresh leaves essential oil (LEO), its volatile fractions (V₁–V₁₀) as well as compound 1 were screened for their antibacterial, antityrosinase, anticholinesterase and anti‐5‐lipoxygenase activities. It was found that the isolated compound 1 exhibited an interesting antibacterial activity against Staphylococcus aureus ATCC 25923 (MIC=32 μg/mL) and Enterococcus faecalis ATCC 29212 (MIC=32 μg/mL) and the highest antityrosinase activity (IC₅₀=13.82±0.87 μg/mL). Compound 1 was also found to be able to strongly inhibit 5‐lipoxygenase with an IC₅₀ value of 59.21±0.85 μg/mL. The bioactivity and drug likeness scores of compound 1 were calculated using Molinspiration software and interpreted, and the structure‐activity relationship (SAR) was discussed with the help of molecular docking analysis.     

Mechanisms of metabisulfite-induced bronchoconstriction: evidence for bradykinin B2-receptor stimulation.

Sodium metabisulfite (MBS) is a food preservative that can trigger bronchoconstriction in asthmatic subjects. Previous studies designed to identify the mechanisms involved in this response have yielded conflicting results. We noted certain similarities between the pharmacology of MBS-induced airway responses and those elicited by bradykinin (BK), another provocating agent in asthmatic subjects. Therefore we used allergic sheep to determine whether MBS-induced bronchoconstriction 1) had a pharmacology similar to that previously seen with BK in this model, including protection by a BK B2-receptor antagonist, NPC-567, and 2) was associated with increased concentrations of immunoreactive kinins in bronchoalveolar lavage. We measured specific lung resistance before and immediately after inhaled buffer and increasing concentrations of MBS (30 breaths of 25, 50, and 100 mg/ml) and calculated the concentration producing 100% increase in specific lung resistance over baseline (PC100). In seven sheep, geometric mean control PC100 was 33.1 mg/ml. Pretreatment with either the anticholinergic agent ipratropium bromide (180 micrograms; PC100 87.1 mg/ml) or the antiasthma drug nedocromil sodium (1 mg/kg aerosol; PC100 97.7 mg/ml) blocked the MBS-induced bronchoconstriction (P less than 0.05), whereas the histamine H1-receptor antagonist chlorpheniramine (2 mg/kg iv) was ineffective. Furthermore the MBS-induced bronchoconstriction was not affected by the neutral endopeptidase inhibitor thiorphan (40 breaths of a 1 mg/ml solution) or the angiotensin-converting enzyme inhibitor enalaprilat (2.5 mg aerosol). In six sheep the MBS-induced bronchoconstriction was completely blocked by NPC-567 (20 breaths, 5 mg/ml aerosol): after treatment with NPC-567 mean PC100 was 100 mg/ml compared with 57.5 mg/ml in the control trial (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

2,4-Diamino-quinazolines as inhibitors of β-catenin/Tcf-4 pathway: Potential treatment for colorectal cancer

The synthesis and SAR of a series of 2,4-diamino-quinazoline derivatives as β-catenin/Tcf-4 inhibitors are described. This series was developed by modifying the initial lead 1, which was identified by screening of our compound library and found to inhibit the β-catenin/Tcf-4 pathway. Replacement of the biphenyl moiety in compound 1 with the N-phenylpiperidine-4-carboxamide chain as in 2, resulted in a number of new analogues, which are potent inhibitors of the β-catenin/Tcf-4 pathway. Compound such as 16k exhibited good cellular potency, solubility, metabolic stability and oral bioavailability.     

Marker-free image registration of electron tomography tilt-series

Background  

Tilt series are commonly used in electron tomography as a means of collecting three-dimensional information from two-dimensional projections. A common problem encountered is the projection alignment prior to 3D reconstruction. Current alignment techniques usually employ gold particles or image derived markers to correctly align the images. When these markers are not present, correlation between adjacent views is used to align them. However, sequential pairwise correlation is prone to bias and the resulting alignment is not always optimal.     

Ab initio and homology based prediction of protein domains by recursive neural networks

Background  

Proteins, especially larger ones, are often composed of individual evolutionary units, domains, which have their own function and structural fold. Predicting domains is an important intermediate step in protein analyses, including the prediction of protein structures.     

Ab initio and template-based prediction of multi-class distance maps by two-dimensional recursive neural networks

Background

Prediction of protein structures from their sequences is still one of the open grand challenges of computational biology. Some approaches to protein structure prediction, especially ab initio ones, rely to some extent on the prediction of residue contact maps. Residue contact map predictions have been assessed at the CASP competition for several years now. Although it has been shown that exact contact maps generally yield correct three-dimensional structures, this is true only at a relatively low resolution (3–4 Å from the native structure). Another known weakness of contact maps is that they are generally predicted ab initio, that is not exploiting information about potential homologues of known structure.

Results

We introduce a new class of distance restraints for protein structures: multi-class distance maps. We show that C _α trace reconstructions based on 4-class native maps are significantly better than those from residue contact maps. We then build two predictors of 4-class maps based on recursive neural networks: one ab initio, or relying on the sequence and on evolutionary information; one template-based, or in which homology information to known structures is provided as a further input. We show that virtually any level of sequence similarity to structural templates (down to less than 10%) yields more accurate 4-class maps than the ab initio predictor. We show that template-based predictions by recursive neural networks are consistently better than the best template and than a number of combinations of the best available templates. We also extract binary residue contact maps at an 8 Å threshold (as per CASP assessment) from the 4-class predictors and show that the template-based version is also more accurate than the best template and consistently better than the ab initio one, down to very low levels of sequence identity to structural templates. Furthermore, we test both ab-initio and template-based 8 Å predictions on the CASP7 targets using a pre-CASP7 PDB, and find that both predictors are state-of-the-art, with the template-based one far outperforming the best CASP7 systems if templates with sequence identity to the query of 10% or better are available. Although this is not the main focus of this paper we also report on reconstructions of C _α traces based on both ab initio and template-based 4-class map predictions, showing that the latter are generally more accurate even when homology is dubious.

Conclusion

Accurate predictions of multi-class maps may provide valuable constraints for improved ab initio and template-based prediction of protein structures, naturally incorporate multiple templates, and yield state-of-the-art binary maps. Predictions of protein structures and 8 Å contact maps based on the multi-class distance map predictors described in this paper are freely available to academic users at the url http://distill.ucd.ie/.