Increased placental expression and maternal serum levels of apoptosis-inducing TRAIL in recurrent miscarriage

AbstractIntroductionRecurrent miscarriage (RM; ≥3 consecutive pregnancy losses) occurs in 1–3% of fertile couples. No biomarkers with high predictive value of threatening miscarriage have been identified. We aimed to profile whole-genome differential gene expression in RM placental tissue, and to determine the protein levels of identified loci in maternal sera in early pregnancy.MethodsGeneChips (Affymetrix®) were used for discovery and Taqman RT-qPCR assays for replication of mRNA expression in placentas from RM cases (n = 13) compared to uncomplicated pregnancies matched for gestational age (n = 23). Concentrations of soluble TRAIL (sTRAIL) and calprotectin in maternal serum in normal first trimester (n = 35) and failed pregnancies (early miscarriage, n = 18, late miscarriage, n = 4; tubal pregnancy, n = 11) were determined using ELISA.ResultsIn RM placentas 30 differentially expressed (with nominal P-value < 0.05) transcripts were identified. Significantly increased placental mRNA expression of TNF-related apoptosis-inducing ligand (TRAIL; P = 1.4 × 10−3; fold-change 1.68) and S100A8 (P = 7.9 × 10−4; fold-change 2.56) encoding for inflammatory marker calprotectin (S100A8/A9) was confirmed by RT-qPCR. When compared to normal first trimester pregnancy (sTRAIL 16.1 ± 1.6 pg/ml), significantly higher maternal serum concentration of sTRAIL was detected at the RM event (33.6 ± 4.3 pg/ml, P = 0.00027), and in pregnant women, who developed an unpredicted miscarriage 2–50 days after prospective serum sampling (28.5 ± 4.4 pg/ml, P = 0.039). Women with tubal pregnancy also exhibited elevated sTRAIL (30.5 ± 3.9 pg/ml, P = 0.035). Maternal serum levels of calprotectin were neither diagnostic nor prognostic to early pregnancy failures (P > 0.05).ConclusionsThe study indicated of sTRAIL as a potential predictive biomarker in maternal serum for early pregnancy complications

Histone H3 Serine 57 and Lysine 56 Interplay in Transcription Elongation and Recovery from S-Phase Stress

Contains fulltext : 84400.pdf (publisher's version ) (Open Access

Microsatellite, blood group and transferrin protein diversity of Estonian dairy cattle breeds

This study investigates genetic diversity within and among three Estonian dairy cattle breeds (Estonian Native, Estonian Red and Estonian Holstein). A total of 36 markers (25 microsatellites, 10 blood group systems and transferrin protein) were investigated and the within-breed diversity was quantified by expected heterozygosity, number of private alleles and mean allelic richness. The population structure was studied by computing the inbreeding coefficients, breed differentiation and relationships were investigated with random drift-based measures and a factorial correspondence analysis. In addition, a neighbour-joining tree was drawn summarising allele sharing distances for 195 individuals of the Estonian breeds, Western Finncattle, and Danish Jersey. The Estonian breeds displayed generally similar levels of within-population diversity. Depending on the set of markers used 6.2 or 4.3% of the total genetic variation can be explained by differences among the breeds. Construction of the tree for individuals revealed a distinctive pattern of grouping for Estonian Holstein, Estonian Red and Danish Jersey, but Estonian Native and Western Finncattle appeared on the same branches. This indicates that the gene pool of Estonian Native largely overlaps with that of Western Finncattle. However, our genetic marker analysis shows that the three Estonian breeds are genetically differentiated, suggesting that the current gene pool of Estonian dairy cattle is diverse.

Microsatellite, blood group and transferrin protein diversity of Estonian dairy cattle breeds

This study investigates genetic diversity within and among three Estonian dairy cattle breeds (Estonian Native, Estonian Red and Estonian Holstein). A total of 36 markers (25 microsatellites, 10 blood group systems and transferrin protein) were investigated and the within-breed diversity was quantified by expected heterozygosity, number of private alleles and mean allelic richness. The population structure was studied by computing the inbreeding coefficients, breed differentiation and relationships were investigated with random drift-based measures and a factorial correspondence analysis. In addition, a neighbour-joining tree was drawn summarising allele sharing distances for 195 individuals of the Estonian breeds, Western Finncattle, and Danish Jersey. The Estonian breeds displayed generally similar levels of within-population diversity. Depending on the set of markers used 6.2 or 4.3% of the total genetic variation can be explained by differences among the breeds. Construction of the tree for individuals revealed a distinctive pattern of grouping for Estonian Holstein, Estonian Red and Danish Jersey, but Estonian Native and Western Finncattle appeared on the same branches. This indicates that the gene pool of Estonian Native largely overlaps with that of Western Finncattle. However, our genetic marker analysis shows that the three Estonian breeds are genetically differentiated, suggesting that the current gene pool of Estonian dairy cattle is diverse.

Milk protein genotypes and milk coagulation properties of Estonian Native cattle

The genetic variation of ás1-, â- and ê-caseins and b-lactoglobulin was determined and their effects on the rennet coagulation properties were examined using 335 milk samples from 118 Estonian Native (EN) cows. We found 16 aggregate casein genotypes (ás1-, â-, ê-caseins), of which four . namely, BB A2A2 AA (21.2%), BB A1A2 AB (16.9%), BB A1A2 AA (14.4%), and BB A2A2 AB (10.2%) occurred among nearly two-thirds of the analysed cows. Aggregate casein genotype had a significant overall effect on rennet coagulation parameters. Better rennet coagulation properties were found for aggregate casein genotypes CC A2A2 AB and BC A1A2 BB, among frequent genotypes for BB A1A2 AB. Of the cattle breeds raised in Estonia, milk from EN had the best coagulation properties and highest frequency of favourable ê-Cn B allele.

Microsatellite, blood group and transferrin protein diversity of Estonian dairy cattle breeds

This study investigates genetic diversity within and among three Estonian dairy cattle breeds (Estonian Native, Estonian Red and Estonian Holstein). A total of 36 markers (25 microsatellites, 10 blood group systems and transferrin protein) were investigated and the within-breed diversity was quantified by expected heterozygosity, number of private alleles and mean allelic richness. The population structure was studied by computing the inbreeding coefficients, breed differentiation and relationships were investigated with random drift-based measures and a factorial correspondence analysis. In addition, a neighbour-joining tree was drawn summarising allele sharing distances for 195 individuals of the Estonian breeds, Western Finncattle, and Danish Jersey. The Estonian breeds displayed generally similar levels of within-population diversity. Depending on the set of markers used 6.2 or 4.3% of the total genetic variation can be explained by differences among the breeds. Construction of the tree for individuals revealed a distinctive pattern of grouping for Estonian Holstein, Estonian Red and Danish Jersey, but Estonian Native and Western Finncattle appeared on the same branches. This indicates that the gene pool of Estonian Native largely overlaps with that of Western Finncattle. However, our genetic marker analysis shows that the three Estonian breeds are genetically differentiated, suggesting that the current gene pool of Estonian dairy cattle is diverse.

Genetic differentiation among commercial and native cattle breeds

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Differences in behavioural effects of amphetamine and dopamine-related gene expression in wild-type and homozygous CCK2 receptor deficient mice

Neuropeptide cholecystokinin (CCK) interacts with dopamine in the regulation of motor activity and motivations. Therefore, in CCK2 receptor deficient mice the behavioural effects of repeated amphetamine administration and changes in dopamine-related gene expression were studied. Four-day amphetamine (1 mg/kg) treatment induced a significantly stronger motor sensitization in homozygous mice compared to their wild-type littermates. However, in the conditioned place preference test the action of amphetamine was more pronounced in wild-type animals. As opposed to wild-type mice, amphetamine (1–3 mg/kg) did not cause a significant conditioned place preference in homozygous mice. The expression of Tyhy gene was elevated in the mesolimbic structures and Drd2 gene was down-regulated in the mesencephalon of saline-treated homozygous mice in comparison with respective wild-type group. Four-day treatment with amphetamine induced a significant increase in the expression of Tyhy in the mesencephalon, striatum and mesolimbic structures of wild-type mice, whereas in homozygous mice a similar change was evident only in the mesencephalon. Also, the expression of Drd1 gene in the striatum and Drd2 gene in the mesolimbic structures of wild-type mice were up-regulated under the influence of amphetamine. In conclusion, the present study established differences in the behavioural effects of amphetamine in wild-type and homozygous mice. The increased tone of dopaminergic projections from the mesencephalon to mesolimbic structures is probably related to increased amphetamine-induced motor sensitization in homozygous mice. The lack of development of up-regulation of Drd1 and Drd2 genes after repeated treatment with amphetamine probably explains the reduced place conditioning in CCK2 receptor deficient mice