Maternal and paternal influences on length of pregnancy

OBJECTIVE: Biological evidence suggests that both mother and fetus are involved in triggering a normal delivery. A tendency of a child to have a gestational age at birth similar to the father's could represent the effect of genes passed from the father to the fetus. Similar tendencies between mother and child could represent maternal genes passed to the fetus, as well as genes to the mother received from the grandmother that affect a woman's capacity to carry a pregnancy. METHODS: The Medical Birth Registry of Norway contains data on all births in Norway from 1967 onward. We identified 77,452 pairs of boys and girls born at term who later became parents and linked their birth data to the birth records for their first child. RESULTS: Gestational age of the child at birth increased on average 0.58 days for each additional week in the father's gestational age (95% confidence interval 0.48-0.67) and 1.22 days for each additional week in the mother's gestational age (1.21-1.32). Gestational age was, however, 0.65 days reduced for each additional kilogram in the father's birth weight, presumably due to more rapid growth of the fetus triggering delivery. CONCLUSION: Initiation of delivery has a fetal component that is heritable (passed from father and mother to child) and an additional maternal component that is also heritable. In addition, a more rapid rate of fetal growth appears to trigger delivery at earlier gestation. LEVEL OF EVIDENCE: II-2.     

Microfibril-associated protein 4 binds to surfactant protein A (SP-A) and colocalizes with SP-A in the extracellular matrix of the lung

Pulmonary surfactant protein A (SP-A) is an oligomeric collectin that recognizes lipid and carbohydrate moieties present on broad range of micro-organisms, and mediates microbial lysis and clearance. SP-A also modulates multiple immune-related functions including cytokine production and chemotaxis for phagocytes. Here we describe the molecular interaction between the extracellular matrix protein microfibril-associated protein 4 (MFAP4) and SP-A. MFAP4 is a collagen-binding molecule containing a C-terminal fibrinogen-like domain and a N-terminal located integrin-binding motif. We produced recombinant MFAP4 with a molecular mass of 36 and 66 kDa in the reduced and unreduced states respectively. Gel filtration chromatography and chemical crosslinking showed that MFAP4 forms oligomers of four dimers. We demonstrated calcium-dependent binding between MFAP4 and human SP-A1 and SP-A2. No binding was seen to recombinant SP-A composed of the neck region and carbohydrate recognition domain of SP-A indicating that the interaction between MFAP4 and SP-A is mediated via the collagen domain of SP-A. Monoclonal antibodies directed against MFAP4 and SP-A were used for immunohistochemical analysis, which demonstrates that the two molecules colocalize both on the elastic fibres in the interalveolar septum and in elastic lamina of pulmonary arteries of chronically inflamed lung tissue. We conclude, that MFAP4 interacts with SP-A via the collagen region in vitro, and that MFAP4 and SP-A colocates in different lung compartments indicating that the interaction may be operative in vivo.     

Cell-compatible covalently reinforced beads obtained from a chemoenzymatically engineered alginate

A chemoenzymatic strategy has been exploited to make covalently linked alginate beads with high stability. This was achieved by grafting mannuronan (alginate with 100% mannuronic acid (M)) with methacrylate moieties and then performing two enzymatic steps converting M to guluronic acid (G) in alternating sequences (MG-blocks) and in G-blocks. In this way a methacrylate grafted alginate with better gel-forming ability was achieved. Covalent bindings were introduced into the beads by using a photoinitiating system that initiated polymerization of the methacrylate moieties. The covalent links were demonstrated by beads remaining intact after treatment with EDTA. The new chemoenzymatic photocrosslinked (CEPC) beads were compatible with cells with low post-encapsulation ability like C2C12 myoblasts and human pancreatic islets. The islets continued secreting insulin after encapsulation. On contrary, cells with a high post-encapsulation proliferative ability like 293-endo cells died within 2-week post-encapsulation. The exceptional stability and the cell compatibility of the new CEPC beads make them interesting as bioreactors for delivering therapeutic proteins in future applications.     

Intergenerational birth weight associations by mother's birth order — The mechanisms behind the paradox: A population-based cohort study

Background

Mother's birth order is inversely associated with offspring birth weight despite positively associated with the mother's own birth weight. The causes behind this relation have not been elucidated.

Aims

To investigate the relation between mother's birth order and birth weight of her offspring, with emphasis on possible mechanisms behind the findings.

Study design

Population based cohort study over two generations.

Subjects

Data were from the Medical Birth Registry of Norway, based on all births in Norway, 1967-2006 (2.3 million births). Units where both mothers and offspring were singletons and offspring were first born were included, forming 272,674 mother-offspring units for the analyses.

Outcome measure

Birth weight in the second generation.

Results

Mother's birth weight increased steadily with increasing birth order from 3369 g for first born to 3538 g for fourth or later born mothers. In contrast, there was a monotonic decrease in offspring mean birth weight with increasing mother's birth order (9.1 g per birth order (95% C.I.; 6.8, 11.4)). First born mothers tended to be older, to have higher education, to more often be married or cohabiting, and to smoke less than later born mothers at the time of their first pregnancy.

Conclusion

The general reduction in mean birth weight among first born mothers was not observed in the next generation. We suggest that first born mothers have the same biologically potential for achieving similar sized offspring as later born mothers, and that social factors account for the inverse relation.     

The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels

Ficolin-2 (L-ficolin), derived from the FCN2 gene, is an innate immunity pattern recognition molecule found in human serum in which inter-individual variation in serum appears to be under genetic control. To validate and extend this finding, we developed a sandwich ELISA for detection of human Ficolin-2 in serum samples and identified FCN2 genotypes with a Taq Man-based minor groove binder assay and by sequencing. Serum samples were applied to gel-permeation chromatography and fractions were analysed by an ELISA, SDS-PAGE and subsequently Western blotting. In 214 Danish blood donors, the median Ficolin-2 serum concentration was determined to 5.4 microg/ml (range: 1.0-12.2 microg/ml). An ELISA, SDS-PAGE and Western blot analysis of gel-permeation chromatography fractions showed that Ficolin-2 comprises a mixture of covalently and non-covalently linked Ficolin-2 oligomers independent of the individual genotypes. The variation in serum concentration was associated with three polymorphisms in the promoter and one polymorphism in the structural part of the FCN2 gene. Further analysis indicated that two particular alleles on the same haplotype determined a low Ficolin-2 concentration. Our results show that inter-individual variation of Ficolin-2 concentration is associated with polymorphisms in the promoter and the structural part of the FCN2 gene.     

Binding and leakage of barium in alginate microbeads

Microbeads of alginate crosslinked with Ca(2+) and/or Ba(2+) are popular matrices in cell-based therapy. The aim of this study was to quantify the binding of barium in alginate microbeads and its leakage under in vitro and accumulation under in vivo conditions. Low concentrations of barium (1 mM) in combination with calcium (50 mM) and high concentrations of barium (20 mM) in gelling solutions were used for preparation of microbeads made of high-G and high-M alginates. High-G microbeads accumulated barium from gelling solution and contained higher concentrations of divalent ions for both low- and high-Ba exposure compared with high-G microbeads exposed to calcium solely and to high-M microbeads for all gelling conditions. Although most of the unbound divalent ions were removed during the wash and culture steps, leakage of barium was still detected during storage. Barium accumulation in blood and femur bone of mice implanted with high-G beads was found to be dose-dependent. Estimated barium leakage relevant to transplantation to diabetic patients with islets in alginate microbeads showed that the leakage was 2.5 times lower than the tolerable intake value given by WHO for high-G microbeads made using low barium concentration. The similar estimate gave 1.5 times higher than is the tolerable intake value for the high-G microbeads made using high barium concentration. To reduce the risk of barium accumulation that may be of safety concern, the microbeads made of high-G alginate gelled with a combination of calcium and low concentration of barium ions is recommended for islet transplantation. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:2939-2947, 2012.     

Decreased material-activation of the complement system using low-energy plasma polymerized poly(vinyl pyrrolidone) coatings

In the current study we investigate the activation of blood complement on medical device silicone rubber and present a plasma polymerized vinyl pyrrolidone (ppVP) coating which strongly decreases surface-activation of the blood complement system. We show that uncoated silicone and polystyrene are both potent activators of the complement system, measured both as activated, deposited C3b and quantifying fluid-phase release of the cleavage fragment C3c. The ppVP coated silicone exhibits approximately 90% reduced complement activation compared to untreated silicone. Quartz crystal microbalance with dissipation (QCM-D) measurements show relatively strong adsorption of blood proteins including native C3 to the ppVP surface, indicating that reduction of complement activation on ppVP is neither a result of low protein adsorption nor lower direct C3-binding, and is therefore possibly a consequence of differences in the adsorbed protein layer composition. The alternative and classical complement pathways are barely detectable on ppVP while the lectin pathway through MBL/ficolin-2 deposition remains active on ppVP suggesting this pathway is responsible for the remaining subtle activation on the ppVP coated surface. The ppVP surface is furthermore characterized physically and chemically using scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR), which indicates preservation of chemical functionality by the applied plasma process. Overall, the ppVP coating shows a potential for increasing complement-compatibility of blood-contacting devices.