PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test

Dynamics and stability in prebiotic information integration:an RNA World model from first principles

The robust coevolution of catalytically active, metabolically cooperating prebiotic RNA replicators were investigated using an RNA World model of the origin of life based on physically and chemically plausible first principles. The Metabolically Coupled Replicator System assumes RNA replicators to supply metabolically essential catalytic activities indispensable to produce nucleotide monomers for their own template replication. Using external chemicals as the resource and the necessary ribozyme activities, Watson-Crick type replication produces complementary strands burdened by high-rate point mutations (insertions, deletions, substitutions). Metabolic ribozyme activities, replicabilities and decay rates are assigned to certain sequence and/or folding (thermodynamical) properties of single-stranded RNA molecules. Short and loosely folded sequences are given replication advantage, longer and tightly folded ones are better metabolic ribozymes and more resistant to hydrolytic decay. We show that the surface-bound MCRS evolves stable and metabolically functional communities of replicators of almost equal lengths, replicabilities and ribozyme activities. Being highly resistant to the invasion of parasitic (non-functional) replicators, it is also stable in the evolutionary sense. The template replication mechanism selects for catalytic “promiscuity”: the two (complementary) strands of the same evolved replicator will often carry more than a single catalytically active motif, thus maximizing functionality in a minimum of genetic information