Complete protein sequence and identification of structural domains of human apolipoprotein B

Epidemiological, pathological and genetic studies show a strong positive correlation between elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol and the risk of premature coronary heart disease. Apolipoprotein (apo) B-100 is the sole protein component of LDL and is the ligand responsible for the receptor-mediated uptake and clearance of LDL from the circulation. Apo B-100 is made by the liver and is essential for the assembly of triglyceride-rich very low-density lipoproteins (VLDL) in the cisternae of the endoplasmic reticulum and for their secretion into the plasma. VLDL transports triglyceride to peripheral muscle and adipose tissue, where the triglyceride is hydrolysed by lipoprotein lipase. The resultant particle, relatively enriched in cholesteryl ester, constitutes LDL. LDL delivers cholesterol to peripheral tissues where it is used for membrane and steroid hormone biosynthesis and to the liver, the only organ which can catabolize and excrete cholesterol. Plasma LDL levels are therefore determined by the balance between their rate of production from VLDL and clearance by the hepatic LDL (apo B/E) receptor pathway. Here we report the complete 4,563-amino-acid sequence of apo B-100 precursor (relative molecular mass (Mr) 514,000 (514K] determined from complementary DNA clones. Numerous lipid-binding structures are distributed throughout the extraordinary length of apo B-100 and must underlie its special functions as a nucleus for lipoprotein assembly and maintenance of plasma lipoprotein integrity. A domain enriched in basic amino-acid residues has been identified as important for the cellular uptake of cholesterol by the LDL receptor pathway.     

Rapid freshening of the deep North Atlantic Ocean over the past four decades

The overflow and descent of cold, dense water from the sills of the Denmark Strait and the Faroe Shetland channel into the North Atlantic Ocean is the principal means of ventilating the deep oceans, and is therefore a key element of the global thermohaline circulation. Most computer simulations of the ocean system in a climate with increasing atmospheric greenhouse-gas concentrations predict a weakening thermohaline circulation in the North Atlantic as the subpolar seas become fresher and warmer, and it is assumed that this signal will be transferred to the deep ocean by the two overflows. From observations it has not been possible to detect whether the ocean's overturning circulation is changing, but recent evidence suggests that the transport over the sills may be slackening. Here we show, through the analysis of long hydrographic records, that the system of overflow and entrainment that ventilates the deep Atlantic has steadily changed over the past four decades. We find that these changes have already led to sustained and widespread freshening of the deep ocean.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

A change in the freshwater balance of the Atlantic Ocean over the past four decades

The oceans are a global reservoir and redistribution agent for several important constituents of the Earth's climate system, among them heat, fresh water and carbon dioxide. Whereas these constituents are actively exchanged with the atmosphere, salt is a component that is approximately conserved in the ocean. The distribution of salinity in the ocean is widely measured, and can therefore be used to diagnose rates of surface freshwater fluxes, freshwater transport and local ocean mixing--important components of climate dynamics. Here we present a comparison of salinities on a long transect (50 degrees S to 60 degrees N) through the western basins of the Atlantic Ocean between the 1950s and the 1990s. We find systematic freshening at both poleward ends contrasted with large increases of salinity pervading the upper water column at low latitudes. Our results extend a growing body of evidence indicating that shifts in the oceanic distribution of fresh and saline waters are occurring worldwide in ways that suggest links to global warming and possible changes in the hydrologic cycle of the Earth.