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.     

Translating molecular discoveries into new therapies for atherosclerosis

Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are beneficial. Furthermore, efforts to understand how risk factors such as high blood pressure, dysregulated blood lipids and diabetes contribute to atherosclerotic disease, as well as to understand the molecular pathogenesis of atherosclerotic plaques, are leading to new targets for therapy.     

The scotopic visual sensitivity of four species of trout: a comparative study

We compared the maximum scotopic visual sensitivity of 4 species of trout from twilight (mesotopic) to fully dark-adapted vision. Scotopic vision is the minimum number of photons to which a fully dark-adapted animal will show a behavioral response. A comparison of visual sensitivity under controlled laboratory conditions showed that brown trout ( Salmo trutta ) and brook trout ( Salvelinus fontinalis ) had maximum scotopic thresholds (1.1 × 10 –4 μmol ? m –2 s –1 , ～0.005 lux) 2 times lower than rainbow trout ( Oncorhyncus mykiss ) and Snake River cutthroat trout ( Oncorhynchus clarki bouvieri ), which did not differ from each other (2.1 × 10 –4 μmol ? m –2 s –1 , ～0.01 lux). A literature review tended to corroborate these results in that brown trout and brook trout were reported to be more active during the night and at twilight than cutthroat trout and rainbow trout. We also measured light intensity within open versus shaded reaches during the day, dusk, and night in 3 Rocky Mountain streams. The scotopic sensitivity of brown trout and brook trout was sufficient to allow foraging during all twilight periods and under average nighttime light intensities in open and shaded reaches, whereas the scotopic sensitivity of rainbow trout and cutthroat trout may restrict their foraging to relatively bright nocturnal conditions (twilight or a moonlit night). Native cutthroat trout restoration efforts may have greater success in open versus shaded stream reaches in the Rocky Mountains and elsewhere.     

The stream–lake ecotone: potential habitat for juvenile endangered June suckers ( Chasmistes liorus )

Potamodromous fish are poorly studied even though they are threatened often by human activities. The June sucker ( Chasmistes liorus ) is an endangered potamodromous species endemic to Utah Lake. Larval June suckers have not been collected from Utah Lake for at least 3 decades. Recruitment appears to be limited by low temperatures and scarce food, resulting in mass starvation of larval June suckers in the stream environment. We compared water temperature, zooplankton food availability, and small fish abundance in the stream and in 3 habitats along the stream&;ndash;lake ecotone (dense emergent vegetation, sparse emergent vegetation, and open lake) to test the hypothesis that all 3 factors would reach a maximum in the dense emergent vegetation of the stream&;ndash;lake ecotone. We used the abundance of fathead minnows in each habitat type as a surrogate for small fish like juvenile June suckers. We found that temperature, food, and fathead minnows reached their maximums in the open lake rather than in vegetated habitats of the stream&;ndash;lake ecotone. The stream had the lowest average temperatures (15.1 &;deg;C) and the lowest zooplankton concentrations (61 ? L &;ndash;1 ) over the growing season. Contrary to expectations, low temperatures (16.9 &;deg;C) and low food abundance (505 ? L &;ndash;1 ) also characterized the densely vegetated habitat, whereas the open lake had the highest temperatures (20.4&;deg; C) and highest concentrations of zooplankton (2353 ? L &;ndash;1 ). Restoration should include a mechanism to transport larval fish through the densely vegetated portion of the stream&;ndash;lake ecotone, which can be hundreds of meters wide, to the warm productive waters of the open lake. The braided planform of the terminal reaches of Hobble Creek should be replaced with shallow riffles to increase mean stream velocity and decrease the transport time of larval June suckers. Los peces potamodromos se han estudiado poco a pesar de que a menudo los amenazan las actividades humanas. El matalote junio ( Chasmistes liorus ) es una especie potamodroma en peligro de extinci&;oacute;n que es end&;eacute;mica del Lago Utah. Hace al menos tres d&;eacute;cadas que no se colectan matalotes larvales del Lago Utah. El reclutamiento parece estar limitado tanto por las temperaturas bajas como por la escasez de alimento, la cual causa una inanici&;oacute;n masiva de matalotes junio larvales en el h&;aacute;bitat fluvial. Comparamos la temperatura del agua, disponibilidad de zooplancton y abundancia de peces peque&;ntilde;os en el arroyo y en tres h&;aacute;bitats a lo largo del ecotono arroyo&;ndash;lago (vegetaci&;oacute;n semisumergida tupida, vegetaci&;oacute;n semisumergida escasa y el lago abierto) para comprobar la hip&;oacute;tesis de que los tres factores alcanzar&;iacute;an su m&;aacute;ximo en la vegetaci&;oacute;n semisumergida tupida del ecotono arroyo&;ndash;lago. Utilizamos la abundancia de la carpita cabezona en cada clase de h&;aacute;bitat como indicador indirecto de peces peque&;ntilde;os como los matalotes junio juveniles. Descubrimos que la temperatura, el alimento y las carpitas cabezonas alcanzaron sus niveles m&;aacute;ximos en el lago abierto y no en los h&;aacute;bitats con vegetaci&;oacute;n del ecotono arroyo&;ndash;lago. El arroyo tuvo las temperaturas promedio m&;aacute;s bajas durante la temporada de crecimiento (15.1 &;deg;C) y concentraciones bajas de zooplancton (61 ? L &;ndash;1 ). Al contrario de lo esperado, el h&;aacute;bitat de vegetaci&;oacute;n tupida tuvo temperaturas bajas (16.9 &;deg;C) y concentraciones bajas de alimento (505 ? L &;ndash;1 ), mientras que el lago abierto tuvo la temperatura m&;aacute;s alta (20.4 &;deg;C) y la mayor concentraci&;oacute;n de zooplancton (2353 ?&;nbsp; L &;ndash;1 ). La restauraci&;oacute;n de esta especie debe incluir alg&;uacute;n mecanismo para transportar los peces larvales a trav&;eacute;s de la parte de vegetaci&;oacute;n tupida del ecotono arroyo&;ndash;lago, la cual puede tener cientos de metros de ancho, a las aguas c&;aacute;lidas y m&;aacute;s productivas del lago abierto. Se debe reemplazar la forma trenzada de los tramos terminales de Hobble Creek con encalladeros para aumentar la velocidad promedio del arroyo y agilizar la traves&;iacute;a de los matalotes junio larvales.     

A novel endothelial-derived lipase that modulates HDL metabolism

High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease. At least 50% of the variation in HDL cholesterol levels is genetically determined, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans. We describe here the cloning and in vivo functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and in vivo effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.