Newly identified loci that influence lipid concentrations and risk of coronary artery disease

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.     

Wing bone stresses in free flying bats and the evolution of skeletal design for flight.

The primary mechanical functions of limb bones are to resist deformation, and hence provide stiff levers against which muscles can act, and to be sufficiently strong to prevent breaking under static or dynamic loads which arise from normal and accidental activities. If bones perform these functions with a minimum amount of material, the energetic costs associated with building, maintaining and transporting the skeleton will be minimized. Appropriate skeletal architecture for minimizing mass while maximizing strength depends on forces imposed on structural elements. In the evolutionary acquisition of flight in the bat lineage, the forelimb skeleton must have come to experience locomotor-forces that differed from those engendered by the terrestrial locomotion of non-flying bat relatives. Here we successfully measure in vivo strain on the wing bones of flying mammals. Our data demonstrate that torsion and shear are unique and crucial features of skeletal biomechanics during flight, and suggest that the evolution of skeletal design in bats and other flying vertebrates may be driven by the need to resist these loads.     

Effect of exogenous ammonium on glutamine synthetase, glutamate synthase, and glutamate dehydrogenase in the root of rice seedling

Root biomass of rice seedlings was increased at lower concentration of exogenous NH ₄ ⁺ , but it was decreased at higher concentration of exogenous NH ₄ ⁺ . The level of free NH ₄ ⁺ in the roots was accumulated gradually with the increase of NH ₄ ⁺ concentration in the nutrient solution. The content of the soluble proteins was essentially constant at higher NH ₄ ⁺ . The activities of glutamine synthetase (GS), NADH-dependent glutamate synthase (NADH-GOGAT), and NADH-dependent glutamate dehydrogenase (NADH-GDH) were risen with exogenous NH ₄ ⁺ concentration at the lower NH ₄ ⁺ concentration range. But the activities of GS and NADH-GOGAT were declined, and the level of NADH-GDH activity was kept constant under higher NH ₄ ⁺ concentration. The GS/GDH ratio suggested that NH ₄ ⁺ was assimilated by GS-GOGAT cycle under lower NH ₄ ⁺ concentration, but NADH-GDH was more important for NH ₄ ⁺ assimilation and detoxifying NH ₄ ⁺ to the tissue cells at the higher NH ₄ ⁺ level. According to the growth and the activity changes of these ammonium-assimilating enzymes of rice seedling roots, 10. 0 μg/mL NH ₄ ⁺ -N in nutrient solution was more suitable to the rice growth. Foundation item: Supported by the National Natural Science Foundation of China (No. 3987052), Natural Science Foundation of Hubei Province and International Rice Research Institute, P.O. Box. 3217, 1271 Makati City, Philippines. Biography: LI Ze-song(1968-), male, Graduate student.     

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.     

A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice

Hemoglobin deficit (hbd) mice carry a spontaneous mutation that impairs erythroid iron assimilation but does not cause other defects. Normal delivery of iron to developing erythroid precursors is highly dependent on the transferrin cycle. Through genetic mapping and complementation experiments, we show that the hbd mutation is an in-frame deletion of a conserved exon of the mouse gene Sec15l1, encoding one of two Sec15 proteins implicated in the mammalian exocyst complex. Sec15l1 is linked to the transferrin cycle through its interaction with Rab11, a GTPase involved in vesicular trafficking. We propose that inactivation of Sec15l1 alters recycling of transferrin cycle endosomes and increases the release of transferrin receptor exocytic vesicles. This in turn decreases erythroid iron uptake. Determining the molecular basis of the hbd phenotype provides new insight into the intricate mechanisms necessary for normal erythroid iron uptake and the function of a mammalian exocyst protein.     

Specific anti-antibodies

Résumé Les anti-anticorps pourraient avoir des applications theérapeutiques dans certains états allergiques, les maladies d'auto-immunisation et dans les greffes des tissues. Les auteurs montrent la possibilité de stimuler la formation des anti-anticorps specifiques contre les anticorps produits par des antigènes relativement simples comme l'albumine, le facteur Rh, le facteur rheumatoïde et la streptolysine 0