hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia

We report the first case of nonimmune hydrops fetalis (NIHF) associated with a recessive, in-frame deletion of V205 in the G protein–coupled receptor, Calcitonin Receptor-Like Receptor (hCALCRL). Homozygosity results in fetal demise from hydrops fetalis, while heterozygosity in females is associated with spontaneous miscarriage and subfertility. Using molecular dynamic modeling and in vitro biochemical assays, we show that the hCLR(V205del) mutant results in misfolding of the first extracellular loop, reducing association with its requisite receptor chaperone, receptor activity modifying protein (RAMP), translocation to the plasma membrane and signaling. Using three independent genetic mouse models we establish that the adrenomedullin–CLR–RAMP2 axis is both necessary and sufficient for driving lymphatic vascular proliferation. Genetic ablation of either lymphatic endothelial Calcrl or nonendothelial Ramp2 leads to severe NIHF with embryonic demise and placental pathologies, similar to that observed in humans. Our results highlight a novel candidate gene for human congenital NIHF and provide structure–function insights of this signaling axis for human physiology

Histological characteristics of singleton placentas delivered before the 28th week of gestation

The placenta is a record of the fetal environment and its examination may provide information about the baby’s subsequent growth and development. We describe the histological characteristics of 947 singleton placentas from infants born between 23 and 27 weeks gestation

Mouse ascites Golgi mucin expression abnormalities in natural cycle endometrial biopsies predict subsequent in vitro fertilization-embryo transfer (IVF-ET) failure in patients with previous IVF-ET failures

We performed a double-blinded retrospective cohort study to determine whether endometrial expression of mouse ascites Golgi mucin in a natural, unmedicated cycle predicts subsequent IVF-ET outcome among women with prior IVF-ET failure and poor pre-embryo quality. We found a statistically significant decrease in clinical pregnancy rate among women with abnormal mouse ascites Golgi expression, a test which was found to have high positive predictive value for failed IVF-ET. ©2006 by American Society for Reproductive Medicine

Persistent economic divergence and institutional dysfunction in post-communist economies: an alternative synthesis

This paper seeks to explain the continuing lack of economic convergence and the persistence of market dysfunctionality, or wild capitalism, in post Communist transformation. An overview of key statistics on economic convergence and market failure are presented. The paper then analyses the causes of malaise through the lens of institutionalist and radical perspectives. In doing so key data is assembled and presented from documents of the international financial institutions and other agencies monitoring crime and corruption. The paper concludes that rather than encourage convergence and tame dysfunctionality, neoliberalism and its offspring of labour market reform has created the conditions for continuing economic divergence and for wild capitalism to survive and thrive

Biosynthesis and turnover of a 34-kDa protein growth factor in human cytotrophoblasts

Recently we isolated a new protein growth factor of 34 kDa from synctial membranes of human placenta. In its polypeptide molecular mass, antigenic structure, receptor binding specificity and partial amino acid sequence, it is unlike several known growth factors, hormones and other proteins. Here we report studies on its biosynthesis and turnover in cultured cytotrophoblasts from term human placenta. Expression of the 34-kDa protein in these cells was studied by immunoprecipitation and Western blot analyses using a highly specific antibody. The experiments have produced the following results. a) Immunostaining and Western blot analyses have demonstrated the presence of immunoreactive 34-kDa protein in isolated cytotrophoblasts. The protein is present in both freshly isolated cells and in cells that have fused in culture to form multinuclear syncytiotrophoblasts. b) Trophoblastic biosynthesis of the protein has been demonstrated by in vitro translation of cellular mRNA and by metabolic labelling experiments with intact cells. c) Pulse-chase experiments show that biosynthesis of the protein does not involve any detectable precursors of higher or lower molecular mass. d) Studies on turnover indicate that the synthesized protein is unusually stable with a half-life of 50–70 h