A study on the minimum number of loci required for genetic evaluation using a finite locus model

For a finite locus model, Markov chain Monte Carlo (MCMC) methods can be used to estimate the conditional mean of genotypic values given phenotypes, which is also known as the best predictor (BP). When computationally feasible, this type of genetic prediction provides an elegant solution to the problem of genetic evaluation under non-additive inheritance, especially for crossbred data. Successful application of MCMC methods for genetic evaluation using finite locus models depends, among other factors, on the number of loci assumed in the model. The effect of the assumed number of loci on evaluations obtained by BP was investigated using data simulated with about 100 loci. For several small pedigrees, genetic evaluations obtained by best linear prediction (BLP) were compared to genetic evaluations obtained by BP. For BLP evaluation, used here as the standard of comparison, only the first and second moments of the joint distribution of the genotypic and phenotypic values must be known. These moments were calculated from the gene frequencies and genotypic effects used in the simulation model. BP evaluation requires the complete distribution to be known. For each model used for BP evaluation, the gene frequencies and genotypic effects, which completely specify the required distribution, were derived such that the genotypic mean, the additive variance, and the dominance variance were the same as in the simulation model. For lowly heritable traits, evaluations obtained by BP under models with up to three loci closely matched the evaluations obtained by BLP for both purebred and crossbred data. For highly heritable traits, models with up to six loci were needed to match the evaluations obtained by BLP.     

Seasonal variation of behavior and brain size in a freshwater fish

1. Teleost fishes occupy a range of ecosystem, and habitat types subject to large seasonal fluctuations. Temperate fishes, in particular, survive large seasonal shifts in temperature, light availability, and access to certain habitats. Mobile species such as lake trout (Salvelinus namaycush) can behaviorally respond to seasonal variation by shifting their habitat deeper and further offshore in response to warmer surface water temperatures during the summer. During cooler seasons, the use of more structurally complex nearshore zones by lake trout could increase cognitive demands and potentially result in a larger relative brain size during those periods. Yet, there is limited understanding of how such behavioral responses to a seasonally shifting environment might shape, or be shaped by, the nervous system.
2. Here, we quantified variation in relative brain size and the size of five externally visible brain regions in lake trout, across six consecutive seasons in two different lakes. Acoustic telemetry data from one of our study lakes were collected during the study period from a different subset of individuals and used to infer relationships between brain size and seasonal behaviors (habitat use and movement rate).
3. Our results indicated that lake trout relative brain size was larger in the fall and winter compared with the spring and summer in both lakes. Larger brains coincided with increased use of nearshore habitats and increased horizontal movement rates in the fall and winter based on acoustic telemetry. The telencephalon followed the same pattern as whole brain size, while the other brain regions (cerebellum, optic tectum, olfactory bulbs, and hypothalamus) were only smaller in the spring.
4. These findings provide evidence that flexibility in brain size could underpin shifts in behavior, which could potentially subserve functions associated with differential habitat use during cold and warm seasons and allow fish to succeed in seasonally variable environments.

     

Comparative study of thylakoid membranes sensitivity for herbicide detection after physical or chemical immobilization

A micro-test using immobilized thylakoid membranes as sensing element in a micro-electrochemical cell has been developed to assess impairment at the level of the light-driven transport of electrons. In this study, thylakoids isolated from spinach leaves were either immobilized by entrapment in poly(vinylalcohol) bearing styrylpyridinium groups or by chemical immobilization in an albumin-glutaraldehyde crosslinked matrix. The two immobilization procedures were compared upon the sensitivity of the immobilized materials to detect nine herbicides targetting photosystem II. Despite the largely differing mode of immobilization, the procedures led to strikingly similar detection capabilities for herbicides. Inherent characteristics of both immobilization procedures are also discussed.     

Mir-190b negatively contributes to the Trypanosoma cruzi- infected cell survival by repressing PTEN protein expression

Chagas disease, which is caused by the intracellular protozoanTrypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.     

The influence of interdomain interactions on the intradomain motions in yeast phosphoglycerate kinase: a molecular dynamics study

A 3-ns molecular dynamics simulation in explicit solvent was performed to examine the inter- and intradomain motions of the two-domain enzyme yeast phosphoglycerate kinase without the presence of substrates. To elucidate contributions from individual domains, simulations were carried out on the complete enzyme as well as on each isolated domain. The enzyme is known to undergo a hinge-bending type of motion as it cycles from an open to a closed conformation to allow the phosphoryl transfer occur. Analysis of the correlation of atomic movements during the simulations confirms hinge bending in the nanosecond timescale: the two domains of the complete enzyme exhibit rigid body motions anticorrelated with respect to each other. The correlation of the intradomain motions of both domains converges, yielding a distinct correlation map in the enzyme. In the isolated domain simulations—in which interdomain interactions cannot occur—the correlation of domain motions no longer converges and shows a very small correlation during the same simulation time. This result points to the importance of interdomain contacts in the overall dynamics of the protein. The secondary structure elements responsible for interdomain contacts are also discussed.     

Haplotype inference in crossbred populations without pedigree information

Background

Current methods for haplotype inference without pedigree information assume random mating populations. In animal and plant breeding, however, mating is often not random. A particular form of nonrandom mating occurs when parental individuals of opposite sex originate from distinct populations. In animal breeding this is called crossbreeding and hybridization in plant breeding. In these situations, association between marker and putative gene alleles might differ between the founding populations and origin of alleles should be accounted for in studies which estimate breeding values with marker data. The sequence of alleles from one parent constitutes one haplotype of an individual. Haplotypes thus reveal allele origin in data of crossbred individuals.

Results

We introduce a new method for haplotype inference without pedigree that allows nonrandom mating and that can use genotype data of the parental populations and of a crossbred population. The aim of the method is to estimate line origin of alleles. The method has a Bayesian set up with a Dirichlet Process as prior for the haplotypes in the two parental populations. The basic idea is that only a subset of the complete set of possible haplotypes is present in the population.

Conclusion

Line origin of approximately 95% of the alleles at heterozygous sites was assessed correctly in both simulated and real data. Comparing accuracy of haplotype frequencies inferred with the new algorithm to the accuracy of haplotype frequencies inferred with PHASE, an existing algorithm for haplotype inference, showed that the DP algorithm outperformed PHASE in situations of crossbreeding and that PHASE performed better in situations of random mating.     

Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of parasite host-cell interaction

Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is a serious health problem in Latin America. During this parasitic infection, the heart is one of the major organs affected. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. When cells are infected with T. cruzi, they develop an inflammatory response, in which cyclooxygenase-2 (COX-2) catalyses rate-limiting steps in the arachidonic acid pathway. However, how the parasite interaction modulates COX-2 activity is poorly understood. In this study, the H9c2 cell line was used as our model and we investigated cellular and biochemical aspects during the initial 48 h of parasitic infection. Oscillatory activity of COX-2 was observed, which correlated with the control of the pro-inflammatory environment in infected cells. Interestingly, subcellular trafficking was also verified, correlated with the control of Cox-2 mRNA or the activated COX-2 protein in cells, which is directly connected with the assemble of stress granules structures. Our collective findings suggest that in the very early stage of the T. cruzi-host cell interaction, the parasite is able to modulate the cellular metabolism in order to survives.     

A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency

Glucosidase I is an important enzyme in N-linked glycoprotein processing, removing specifically distal alpha-1,2-linked glucose from the Glc3Man9GlcNAc2 precursor after its en bloc transfer from dolichyl diphosphate to a nascent polypeptide chain in the endoplasmic reticulum. We have identified a glucosidase I defect in a neonate with severe generalized hypotonia and dysmorphic features. The clinical course was progressive and was characterized by the occurrence of hepatomegaly, hypoventilation, feeding problems, seizures, and fatal outcome at age 74 d. The accumulation of the tetrasaccharide Glc(alpha1-2)Glc(alpha1-3)Glc(alpha1-3)Man in the patient's urine indicated a glycosylation disorder. Enzymological studies on liver tissue and cultured skin fibroblasts revealed a severe glucosidase I deficiency. The residual activity was <3% of that of controls. Glucosidase I activities in cultured skin fibroblasts from both parents were found to be 50% of those of controls. Tissues from the patient subjected to SDS-PAGE followed by immunoblotting revealed strongly decreased amounts of glucosidase I protein in the homogenate of the liver, and a less-severe decrease in cultured skin fibroblasts. Molecular studies showed that the patient was a compound heterozygote for two missense mutations in the glucosidase I gene: (1) one allele harbored a G-->C transition at nucleotide (nt) 1587, resulting in the substitution of Arg at position 486 by Thr (R486T), and (2) on the other allele a T-->C transition at nt 2085 resulted in the substitution of Phe at position 652 by Leu (F652L). The mother was heterozygous for the G-->C transition, whereas the father was heterozygous for the T-->C transition. These base changes were not seen in 100 control DNA samples. A causal relationship between the alpha-glucosidase I deficiency and the disease is postulated.