Optimization of genomic selection training populations with a genetic algorithm

In this article, we imagine a breeding scenario with a population of individuals that have been genotyped but not phenotyped. We derived a computationally efficient statistic that uses this genetic information to measure the reliability of genomic estimated breeding values (GEBV) for a given set of individuals (test set) based on a training set of individuals. We used this reliability measure with a genetic algorithm scheme to find an optimized training set from a larger set of candidate individuals. This subset was phenotyped to create the training set that was used in a genomic selection model to estimate GEBV in the test set. Our results show that, compared to a random sample of the same size, the use of a set of individuals selected by our method improved accuracies. We implemented the proposed training selection methodology on four sets of data on Arabidopsis, wheat, rice and maize. This dynamic model building process that takes genotypes of the individuals in the test sample into account while selecting the training individuals improves the performance of genomic selection models.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0116-6) contains supplementary material, which is available to authorized users.     

Sequence-specific backbone 1H, 13C and 15N assignments of the catalytic domain of the Escherichia coli protein tyrosine kinase,Wzc

Protein tyrosine kinases in bacteria are structurally and functionally distinct from their eukaryotic counterparts. The largest family of bacterial tyrosine kinases, the BY-kinase family, is highly conserved in Gram-negative and Gram-positive species, and plays a central role in biofilm and capsule formation. In Escherichia coli the BY-kinase, Wzc, is a critical component of the machinery responsible for the synthesis and export of the exo-polysaccharide colanic acid, a key constituent of biofilms. Here we present the main-chain ¹H^N, ¹⁵N, ¹³C′ and ¹³C_α, side-chain ¹³C_β resonance assignments for a construct that encodes the entire 274-residue cytosolic catalytic domain of Wzc.     

Gene therapy for inherited retinal degenerations

Gene therapy is quickly becoming a reality applicable in the clinic for inherited retinal diseases. Progress over the past decade has moved proof-of-concept gene therapies from bench to bedside. The remarkable success in safety and efficacy, in the phase I/II clinical trials for the form of the severe childhood-onset blindness, Leber's Congenital Amaurosis (LCA) type II (due to mutations in the RPE65 gene) generated significant interest and opened up possibilities for a new era of retinal gene therapies. Success in these clinical trials was due to combining the favorable features of both the retina as a target organ and adeno-associated virus (AAV) as a vector. The retina offers several advantages for gene therapy approaches. It is an anatomically defined structure that is readily accessible for therapy and has some degree of immune privilege, making it suitable for application of viral vectors. AAV, on the other hand, is a non-pathogenic helper dependent virus that has little immunogenicity. This viral vector transduces quiescent cells efficiently and thanks to its small size diffuses well in the interneural matrix, making it suitable for applications in neural tissue. Building on this initial clinical success with LCA II, we have now many opportunities to extend this proof-of-concept to other retinal diseases. This article will discuss what are some of the most imminent targets for such therapies and what are the challenges that we face in moving these therapies to the clinic.     

Hepatoprotective potential of Ferula communis extract for carbon tetrachloride induced hepatotoxicity and oxidative damage in rats

ABSTRACT

We investigated the hepatoprotective potential of Ferula communis extract for CCI₄ induced liver damage. We used six groups of rats: group 1, untreated control; group 2, CCl₄ treated (hepatotoxic); group 3, treated with 150 mg/kg F. communis; group 4, treated with 300 mg/kg F. communis; group 5, treated with CCl₄ + 150 mg/kg F. communis; and group 6, treated with CCl₄ + 300 mg/kg F. communis. Liver damage was produced by injection of 1 ml/kg CCI₄ twice/week. Extracts of F. communis, 150 and 300 mg/kg/day, were administered for 8 weeks. The effects of F. communis were assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and total bilirubin (T-BIL) levels, and the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the liver. The histology and immunohistochemistry of liver tissue were evaluated using hematoxylin and eosin staining, and caspase 3 and 8-OHdG immunostaining. F. communis extract produced significant reductions in elevated levels of ALT, AST, GGT and T-BIL and increased levels of GPx and SOD in rats treated with CCl₄. F. communis extract decreased CCl₄ induced 8-OHdG formation and caspase 3 activation significantly in hepatocytes, especially at the 150 mg/kg dose. Our findings demonstrate the potential efficacy of F. communis for attenuating CCl₄ induced hepatotoxicity and oxidative damage.     

Association with Leptin Gene c.-2548 G>A Polymorphism,Serum Leptin Levels,and Body Mass Index in Turkish Obese Patients

Leptin is a protein hormone which plays a critical role in the regulation of both body-weight through reducing food intake and stimulating energy expenditure. Several polymorphisms in leptin gene (LEP), which encodes for leptin, have been described. However, its association with obesity is still controversial. Therefore, in the present study, we aimed to investigate whether LEP c.-2548 G>A polymorphism was associated with serum leptin levels, lipid parameters, and body mass index in Turkish obese patients. Forty-seven obese patients and 48 healthy individuals were included in the study. Blood samples were collected for DNA extraction. LEP c.-2548 G>A polymorphism were detected using polymerase chain reaction–restriction fragment length polymorphism technique. Serum leptin levels and lipid parameters were measured by ELISA and enzyme colorimetric assay techniques, respectively. GA or AA genotypes and A allele carrier frequencies of the c.-2548 G>A polymorphism in the LEP were higher in obese (38.3, 34.0 and 72.3 %) when compared with controls (14.6, 12.5, and 27.1 %; p = 0.011, 0.016, and 0.002, respectively). On the other hand, AA or AG genotypes were also related to increased serum leptin levels (p < 0.001) and body mass index (p < 0.0001). All these consequences showed that LEP -2548 AA or AG genotypes are important predictors for increased levels of leptin and BMI in Turkish obese patients and it may be a useful marker for obesity risk in our population.     

The investigation of glutamate transporter 1 (GLT-1) degradation pathway in glioblastoma cells

Molecular Biology Reports - Glioblastoma multiform is a primary brain tumor derived from glial cells. The aim of this study is to investigate how glutamate metabolism is regulated by glutamate...     

The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats

Coumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl₄) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague–Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl₄, when compared to control values. Similarly, administration of CCl₄ increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg⁻¹, orally) and scoparone (35 mg kg⁻¹, orally) significantly prevented CCl₄-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg⁻¹) and coumarin (30 mg kg⁻¹) had no effect against CCl₄-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress.     

Altered hematological and immunological parameters in silver catfish (Rhamdia quelen) following short term exposure to sublethal concentration of glyphosate

Using agrichemicals to control unwanted species has become a necessary and common worldwide practice to improve crop production. Although most currently used agrichemicals are considered relatively safe, continuous usage contributes for soil and water contamination and collateral toxic effects on aquatic species. Few studies correlated the presence of agrichemicals on fish blood cells and natural immune system. Thus, in this study, silver catfish (Rhamdia quelen) were exposed to sublethal concentrations (10% of the LC(50-96 h)) of a glyphosate based herbicide and hematological and natural immune system parameters were evaluated. Silver catfish fingerlings exposed to glyphosate for 96 h had a significant reduction on blood erythrocytes, thrombocytes, lymphocytes and total leukocytes in contrast to a significant increase in the number of immature circulating cells. The effect of glyphosate on natural immune system was evaluated after 24h or 10 days exposure by measuring the phagocytic index of coelomic cells, and lysozyme, total peroxidase, bacteria agglutination, bactericidal activity and natural complement hemolytic activity in the serum of fingerlings. A significant reduction on phagocytic index, serum bacteria agglutination and total peroxidase was observed only after 24h exposure to glyphosate. In contrast, fingerlings exposed to glyphosate for 10 days had a significant lower serum bacteria agglutination and lysozyme activity. Glyphosate had no effect on serum bactericidal and complement natural hemolytic activity after 24h or 10 days exposure. Nonetheless, the information obtained in this study indicates that glyphosate contaminated water contributes to alter blood cells parameters and to reduce the activity of natural immune components important to mediate fish resistance to infecting microorganisms.