MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome

Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, syndactyly and cardiac defect. We show here that heterozygous mutations in the gene MYCN are present in Feingold syndrome. All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain growth in humans are tightly regulated by MYCN dosage.     

Unravelling the signal-transduction network in B lymphocytes

The Alliance for Cellular Signaling has chosen the mouse B lymphocyte as a model system to understand basic principles that govern cellular signalling. Progress to that end has focused initially on establishing a reproducible experimental cell system and characterizing essential signalling responses. Although unravelling this complex network will take years, findings revealed in the interim will prove immensely useful to the scientific community at large.     

Recent mass balance of polar ice sheets inferred from patterns of global sea-level change

Global sea level is an indicator of climate change, as it is sensitive to both thermal expansion of the oceans and a reduction of land-based glaciers. Global sea-level rise has been estimated by correcting observations from tide gauges for glacial isostatic adjustment--the continuing sea-level response due to melting of Late Pleistocene ice--and by computing the global mean of these residual trends. In such analyses, spatial patterns of sea-level rise are assumed to be signals that will average out over geographically distributed tide-gauge data. But a long history of modelling studies has demonstrated that non-uniform--that is, non-eustatic--sea-level redistributions can be produced by variations in the volume of the polar ice sheets. Here we present numerical predictions of gravitationally consistent patterns of sea-level change following variations in either the Antarctic or Greenland ice sheets or the melting of a suite of small mountain glaciers. These predictions are characterized by geometrically distinct patterns that reconcile spatial variations in previously published sea-level records. Under the--albeit coarse--assumption of a globally uniform thermal expansion of the oceans, our approach suggests melting of the Greenland ice complex over the last century equivalent to -0.6 mm yr(-1) of sea-level rise.     

Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins

Plasma high density lipoproteins (HDL) are a negative risk factor for atherosclerosis. Increased HDL is sometimes clustered in families, but a genetic basis has never been clearly documented. The plasma cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from HDL to other lipoproteins and therefore might influence HDL levels. Using monoclonal antibodies, we show that CETP is absent in two Japanese siblings who have markedly increased and enlarged HDL. Furthermore, they are homozygous for a point mutation in the 5'-splice donor site of intron 14 of the gene for CETP, a change that is incompatible with normal splicing of pre-messenger RNA. The results indicate that the family has an inherited deficiency of CETP due to a gene splicing defect, and illustrate the key role that CETP has in human HDL metabolism.