A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction

Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group.     

A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria

Many biological processes are coupled to ATP hydrolysis. We describe here a class of closely related ATP-binding proteins, from several bacterial species, which are associated with a variety of cellular functions including membrane transport, cell division, nodulation in Rhizobium and haemolysin export. These proteins comprise a family of structurally and functionally related subunits which share a common evolutionary origin, bind ATP and probably serve to couple ATP hydrolysis to each of these biological processes. This finding suggests a specific role for ATP in cell division, nodulation during nitrogen fixation and protein export, and allows us to assign a probable function to one of the protein components from each of these systems.     

The formation of cubic ice under conditions relevant to Earth's atmosphere

An important mechanism for ice cloud formation in the Earth's atmosphere is homogeneous nucleation of ice in aqueous droplets, and this process is generally assumed to produce hexagonal ice. However, there are some reports that the metastable crystalline phase of ice, cubic ice, may form in the Earth's atmosphere. Here we present laboratory experiments demonstrating that cubic ice forms when micrometre-sized droplets of pure water and aqueous solutions freeze homogeneously at cooling rates approaching those found in the atmosphere. We find that the formation of cubic ice is dominant when droplets freeze at temperatures below 190 K, which is in the temperature range relevant for polar stratospheric clouds and clouds in the tropical tropopause region. These results, together with heat transfer calculations, suggest that cubic ice will form in the Earth's atmosphere. If there were a significant fraction of cubic ice in some cold clouds this could increase their water vapour pressure, and modify their microphysics and ice particle size distributions. Under specific conditions this may lead to enhanced dehydration of the tropopause region.     

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.     

Progress and challenges for malaria vaccines

Malaria causes much physical and economic hardship in tropical regions, particularly in communities where medical care is rudimentary. Should a vaccine be developed, it is the residents of these areas that stand to benefit the most. But the vaccine, which has been promised to be 'just round the corner' for many years, remains elusive. It is important to ask why this is so, when effective vaccines exist for many other infectious diseases. What are the reasons for the slow rate of progress, and what has been learned from the first clinical trials of candidate malaria vaccines? What are the remaining challenges, and what strategies can be pursued to address them?