Organoselenium transition metal complexes as promising candidates in medicine area.

The medicinal properties of transition metal complexes are greatly influenced by the nature and physico-chemical features of the ligand present in the complex structure. Due to the unique biological properties of the organoselenium compounds reflected in the variety of pharmacological activities (such as antioxidative, antiviral, antimicrobial and anticancer), the last years have brought increased interest for their use as a ligands compounds in the design and syntheses of range of transition metal-based coordination compounds that have been explored as antitumor and antimicrobial agents. Our aim in this review is to provide the overview of an recent development of the transition metal complexes bearing organoselenium ligands in the structure that could be promising choice for the treatment of various diseases, particularly cancer and infective diseases. For this purpose, the complexes of Co, Ni, Cu, Zn, Ru, Pd, Pt, Au and Sn as the most explored examples will be included and discussed.

Tryptamine-Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties.

Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine-derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p-nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT-116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC-5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT-DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.

Assessing the genetic background and genomic relatedness of red cattle populations originating from Northern Europe.

BACKGROUND: Local cattle breeds need special attention, as they are valuable reservoirs of genetic diversity. Appropriate breeding decisions and adequate genomic management of numerically smaller populations are required for their conservation. At this point, the analysis of dense genome-wide marker arrays provides encompassing insights into the genomic constitution of livestock populations. We have analyzed the genetic characterization of ten cattle breeds originating from Germany, The Netherlands and Denmark belonging to the group of red dairy breeds in Northern Europe. The results are intended to provide initial evidence on whether joint genomic breeding strategies of these populations will be successful. RESULTS: Traditional Danish Red and Groningen White-Headed were the most genetically differentiated breeds and their populations showed the highest levels of inbreeding. In contrast, close genetic relationships and shared ancestry were observed for the populations of German Red and White Dual-Purpose, Dutch Meuse-Rhine-Yssel, and Dutch Deep Red breeds, reflecting their common histories. A considerable amount of gene flow from Red Holstein to German Angler and to German Red and White Dual-Purpose was revealed, which is consistent with frequent crossbreeding to improve productivity of these local breeds. In Red Holstein, marked genomic signatures of selection were reported on chromosome 18, suggesting directed selection for important breeding goal traits. Furthermore, tests for signatures of selection between Red Holstein, Red and White Dual-Purpose, and Meuse-Rhine-Yssel uncovered signals for all investigated pairs of populations. The corresponding genomic regions, which were putatively under different selection pressures, harboured various genes which are associated with traits such as milk and beef production, mastitis and female fertility. CONCLUSIONS: This study provides comprehensive knowledge on the genetic constitution and genomic connectedness of divergent red cattle populations in Northern Europe. The results will help to design and optimize breeding strategies. A joint genomic evaluation including some of the breeds studied here seems feasible.

Factors affecting accuracy of estimated effective number of chromosome segments for numerically small breeds.

For numerically small breeds, obtaining a sufficiently large breed-specific reference population for genomic prediction is challenging or simply not possible, but may be overcome by adding individuals from another breed. To prioritize among available breeds, the effective number of chromosome segments (Me ) can be used as an indicator of relatedness between individuals from different breeds. The Me is also an important parameter in determining the accuracy of genomic prediction. The Me can be estimated both within a population and between two populations or breeds, as the reciprocal of the variance of genomic relationships. However, the threshold for number of individuals needed to accurately estimate within or between populations Me is currently unknown. It is also unknown if a discrepancy in number of genotyped individuals in two breeds affects the estimates of Me between populations. In this study, we conducted a simulation that mimics current domestic cattle populations in order to investigate how estimated Me is affected by number of genotyped individuals, single-nucleotide polymorphism (SNP) density and pedigree availability. Our results show that a small sample of 10 genotyped individuals may result in substantial over or underestimation of Me . While estimates of within population Me were hardly affected by SNP density, between population Me values were highly dependent on the number of available SNPs, with higher SNP densities being able to detect more independent chromosome segments. When subtracting pedigree from genomic relationships before computing Me , estimates of within population Me were three to four times higher than estimates with genotypes only; however, between Me estimates remained the same. For accurate estimation of within and between population Me , at least 50 individuals should be genotyped per population. Estimates of within Me were highly affected by whether pedigree was used or not. For within Me , even the smallest SNP density (~11k) resulted in accurate representation of family relationships in the population; however, for between Me , many more markers are needed to capture all independent segments.

Color stability of bulk-fill and universal composite restorations with dissimilar dentin replacement materials.

OBJECTIVE: To determine color changes in bulk-fill composite and universal composite restorations with dissimilar dentin replacement materials in extracted teeth after staining in red wine. MATERIALS AND METHODS: Cylindrical, 4 mm deep, class I cavities were prepared in 140 human molars. Bottom 2 mm was restored with Biodentine (Septodont), everX posterior (GC) or experimental HAP inserts. Each dentin replacement material was covered with a 2-mm layer of a universal composite Filtek Z250 or Z550 (3M ESPE) or Gradia Posterior (GC). Groups combining top composite layer and the underlying dentin replacement were designated as "composite_dentin replacement." Filtek Bulk Fill (3M ESPE) and Tetric EvoCeram Bulk Fill (Ivoclar Vivadent) were placed as a single 4-mm layer. Color measurements were performed using Vita Easyshade 4.0 (Vita Zahnfabrik) initially and after 48-hours storage in red wine at 37°C. RESULTS: Color differences (ΔEoo ) ranged between 2.1 ± 0.7 (Z250_HAP) and 7.8 ± 1.1 (Z550_everX). EverX resulted in higher ΔEoo of the overlying composite than HAP (P < .001) and Biodentine (P = .006). Generally, ΔEoo was affected more by decreasing lightness (ΔL') than changes in chroma (ΔC'). CONCLUSIONS: EverX resulted in higher ΔEoo of the restoration than Biodentine and experimental HAP after staining in red wine. No significant differences in ΔEoo may be expected in different composites with the same underlying dentin replacement material. The same was generally true for bulk-fill and universal composites. CLINICAL SIGNIFICANCE: Similar extent of color changes may be expected in bulk-fill and universal composites. Highly translucent everX might exhibit greater color differences irrespective of the capping composite than non-translucent materials. Clinicians have a wider choice of composite materials to cover a particular dentin replacement material, for example, everX or Biodentine, as similar color differences may be expected in various overlying composite brands.

Modelling the co-evolution of indirect genetic effects and inherited variability.

When individuals interact, their phenotypes may be affected not only by their own genes but also by genes in their social partners. This phenomenon is known as Indirect Genetic Effects (IGEs). In aquaculture species and some plants, however, competition not only affects trait levels of individuals, but also inflates variability of trait values among individuals. In the field of quantitative genetics, the variability of trait values has been studied as a quantitative trait in itself, and is often referred to as inherited variability. Such studies, however, consider only the genetic effect of the focal individual on trait variability and do not make a connection to competition. Although the observed phenotypic relationship between competition and variability suggests an underlying genetic relationship, the current quantitative genetic models of IGE and inherited variability do not allow for such a relationship. The lack of quantitative genetic models that connect IGEs to inherited variability limits our understanding of the potential of variability to respond to selection, both in nature and agriculture. Models of trait levels, for example, show that IGEs may considerably change heritable variation in trait values. Currently, we lack the tools to investigate whether this result extends to variability of trait values. Here we present a model that integrates IGEs and inherited variability. In this model, the target phenotype, say growth rate, is a function of the genetic and environmental effects of the focal individual and of the difference in trait value between the social partner and the focal individual, multiplied by a regression coefficient. The regression coefficient is a genetic trait, which is a measure of cooperation; a negative value indicates competition, a positive value cooperation, and an increasing value due to selection indicates the evolution of cooperation. In contrast to the existing quantitative genetic models, our model allows for co-evolution of IGEs and variability, as the regression coefficient can respond to selection. Our simulations show that the model results in increased variability of body weight with increasing competition. When competition decreases, i.e., cooperation evolves, variability becomes significantly smaller. Hence, our model facilitates quantitative genetic studies on the relationship between IGEs and inherited variability. Moreover, our findings suggest that we may have been overlooking an entire level of genetic variation in variability, the one due to IGEs.

Genetic parameters for uniformity of harvest weight and body size traits in the GIFT strain of Nile tilapia.

BACKGROUND: Animal breeding programs have been very successful in improving the mean levels of traits through selection. However, in recent decades, reducing the variability of trait levels between individuals has become a highly desirable objective. Reaching this objective through genetic selection requires that there is genetic variation in the variability of trait levels, a phenomenon known as genetic heterogeneity of environmental (residual) variance. The aim of our study was to investigate the potential for genetic improvement of uniformity of harvest weight and body size traits (length, depth, and width) in the genetically improved farmed tilapia (GIFT) strain. In order to quantify the genetic variation in uniformity of traits and estimate the genetic correlations between level and variance of the traits, double hierarchical generalized linear models were applied to individual trait values. RESULTS: Our results showed substantial genetic variation in uniformity of all analyzed traits, with genetic coefficients of variation for residual variance ranging from 39 to 58 %. Genetic correlation between trait level and variance was strongly positive for harvest weight (0.60 ± 0.09), moderate and positive for body depth (0.37 ± 0.13), but not significantly different from 0 for body length and width. CONCLUSIONS: Our results on the genetic variation in uniformity of harvest weight and body size traits show good prospects for the genetic improvement of uniformity in the GIFT strain. A high and positive genetic correlation was estimated between level and variance of harvest weight, which suggests that selection for heavier fish will also result in more variation in harvest weight. Simultaneous improvement of harvest weight and its uniformity will thus require index selection.

Tyramine Derivatives as Versatile Pharmacophores With Potent Biological Properties: Sex Hormone-Binding Globulin Inhibition, Colon Cancer Antimigration, and Antimicrobial Activity.

Guided by the idea that the presence of a heterocyclic aromatic core and tyramine moiety, under the umbrella of a single molecular scaffold could bring interesting biological properties, herein we present synthesis, characterization, with two crystal structures reported, and biological evaluation of some tyramine derivates. Cytotoxic and antimigratory potential was addressed by using a colorectal cancer cell line as a model system. Although possessing no cytotoxic effects, two compounds have shown strong antimigratory potential in low doses, with no effect on healthy MRC-5 cells. Evaluation of their antimicrobial activities suggested prominent antimicrobial activity, where Compound 4 outperformed streptomycin against Escherichia coli and Proteus mirabilis. Hormone-dependent types of cancer, such as prostate, ovary, and breast, are highly dependent on human sex hormone-binding globulin (SHBG) blood levels. A molecular docking study has shown that 1 has high affinity to bind and therefore compete with natural steroids for the SHBG steroid-binding site. DNA-binding study have shown that 4 interacts with CT-DNA in a groove-binding mode. In silico ADME/T study revealed that all compounds have suitable physicochemical properties for oral bioavailability and druglikeness, while toxicity tests for 1, 4, and 6 suggested potential for mutagenicity (4, 6), hepatotoxicity (6), and skin sensation (1).

Capturing indirect genetic effects on phenotypic variability: Competition meets canalization.

Phenotypic variability of a genotype is relevant both in natural and domestic populations. In the past two decades, variability has been studied as a heritable quantitative genetic trait in its own right, often referred to as inherited variability or environmental canalization. So far, studies on inherited variability have only considered genetic effects of the focal individual, that is, direct genetic effects on inherited variability. Observations from aquaculture populations and some plants, however, suggest that an additional source of genetic variation in inherited variability may be generated through competition. Social interactions, such as competition, are often a source of Indirect Genetic Effects (IGE). An IGE is a heritable effect of an individual on the trait value of another individual. IGEs may substantially affect heritable variation underlying the trait, and the direction and magnitude of response to selection. To understand the contribution of IGEs to evolution of environmental canalization in natural populations, and to exploit such inherited variability in animal and plant breeding, we need statistical models to capture this effect. To our knowledge, it is unknown to what extent the current statistical models commonly used for IGE and inherited variability capture the effect of competition on inherited variability. Here, we investigate the potential of current statistical models for inherited variability and trait values, to capture the direct and indirect genetic effects of competition on variability. Our results show that a direct model of inherited variability almost entirely captures the genetic sensitivity of individuals to competition, whereas an indirect model of inherited variability captures the cooperative genetic effects of individuals on their partners. Models for trait levels, however, capture only a small part of the genetic effects of competition. The estimation of direct and indirect genetic effects of competition, therefore, is possible with models for inherited variability but may require a two-step analysis.

Optical properties of composite restorations influenced by dissimilar dentin restoratives.

OBJECTIVES: To evaluate optical properties (color and translucency) of 'sandwich' restorations of resin-based composites and esthetically unfavorable dentin restoratives. METHODS: Cylindrical 'dentin' specimens (8mm in diameter and 2mm thick, N=5/group) were prepared using EverX Posterior (GC), Biodentine (Septodont), experimental hydroxyapatite (HAP) or conventional composites (Gradia Direct Posterior, GC; Filtek Z250 and Filtek Z500, 3M ESPE). Capping 'enamel' layers were prepared using composites (Gradia Direct Posterior, Filtek Z250 or Z550) of A1 or A3 shade and the following thickness: 0.6, 1 or 2mm. Color (ΔE) and translucency parameter (TP) were determined using a spectrophotometer (VITA Easyshade Advance 4.0, VITA Zahnfabrik). Data were statistically analyzed using analysis of variance with Tukey's post-hoc tests (α=0.05). RESULTS: TP was greatly affected by layer thickness, whilst ΔE depended on shade and layer thickness of the capping composite. HAP and Biodentine showed significantly lower TP and higher ΔE (deviation from 'ideal white') than composites (p<0.05). Greater TP was seen in EverX_composite groups than in corresponding control groups of the same shade and thickness. TP of composites combined with Biodentine or HAP was below 2, lower than the corresponding control groups (p<0.05). Within-group differences of ΔE were greatest in HAP_composite groups. EverX_Gradia and EverX_FiltekZ250 combinations showed the most comparable ΔE with the control groups. SIGNIFICANCE: A 2mm thick layer of composite covering dentin restoratives with unfavorable esthetics is recommended for a final 'sandwich' restoration that is esthetically comparable to a conventional, mono-composite control restoration.

Refractive indices of unfilled resin mixtures and cured composites related to color and translucency of conventional and low-shrinkage composites.

This study correlated the refractive indices (RIs) of unfilled resin mixtures and resin-based composites (RBCs) with color and translucency of conventional and low-shrinkage RBCs. Unfilled resin mixtures based on different ratios of conventional monomers Bisphenol A-glycidyl-methacrylate (BisGMA)/triethyleneglycol-dimethacrylate (TEGDMA) and urethane-dimethacrylate (UDMA)/TEGDMA and a low-shrinkage monomer FIT-852 (FIT, Esstech Inc.)/TEGDMA were used to prepare model RBCs, containing 30 wt % of the organic matrix and 70 wt % of silanated barium-glass fillers (n = 1.553, Esstech Inc.). The RIs of resins were measured on an ABBE refractometer, those of cured RBCs using the Becke-line method in immersion oils. Color and translucency were determined using an AvaSpec-2048 (Avantes BV) spectrometer. The RIs of unfilled resin mixtures decreased with increasing amounts of TEGDMA. Cured RBCs had higher RIs than their respective resin mixtures. BisGMA-based composites were more translucent with significantly lower L* values than FIT- and UDMA-based RBCs. The RIs of unfilled resins positively correlated with cured RBCs (p = 0.001), as did the RIs with translucency (p = 0.001) and color (p = 0.008). Resin mixtures and corresponding RBCs based on UDMA and its modified low-shrinkage version, FIT, showed similar optical properties. The RIs of unfilled resins appeared to be good predictors of the RIs of cured RBCs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 7-13, 2017.