Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)

Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.     

In situ Os isotopes in abyssal peridotites bridge the isotopic gap between MORBs and their source mantle

Abyssal peridotites are assumed to represent the mantle residue of mid-ocean-ridge basalts (MORBs). However, the osmium isotopic compositions of abyssal peridotites and MORB do not appear to be in equilibrium, raising questions about the cogenetic relationship between those two reservoirs. However, the cause of this isotopic mismatch is mainly due to a drastic filtering of the data based on the possibility of osmium contamination by sea water. Here we present a detailed study of magmatic sulphides (the main carrier of osmium) in abyssal peridotites and show that the 187Os/188Os ratio of these sulphides is of primary mantle origin and can reach radiogenic values suggesting equilibrium with MORB. Thus, the effect of sea water on the osmium systematics of abyssal peridotites has been overestimated and consequently there is no true osmium isotopic gap between MORBs and abyssal peridotites.     

A receptor for phosphatidylserine-specific clearance of apoptotic cells

cytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally. The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized. Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny.     

Dissociation of obesity,hypercholesterolemia and diabetes from atherosclerosis in ob/ob mice

Summary Genetically obese, diabetic and hypercholesterolemic C57BL/6J-ob/ob mice were placed on Purina Laboratory Chow containing 2% cholesterol for up to 4 months. They developed higher plasma cholesterol levels and accumulated an increased quantity of cholesterol in the liver but failed to develop atherosclerotic lesions in the aorta as would be expected in an obese, diabetic and hypercholesterolemic human adult.Acknowledgments. We wish to thank Mr. Willis M. Overton for his excellent technical assistance.