Disparate effects of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid in vascular endothelial and smooth muscle cells and in cardiomyocytes

The expression and activity of the arachidonic acid-metabolizing enzyme leukocyte-type 12-lipoxygenase (12-LO) are augmented in cultured vascular endothelial and smooth muscle cells exposed to high glucose concentrations and in blood vessels of diabetic animals. The product of this enzyme, 12-hydroxyeicosatetraenoic acid (12-HETE), evokes two types of interactions in these cells: on one hand it acts as a pro-inflammatory factor that contributes to the initiation and progression of atherosclerotic lesions. Yet on the other, it protects the same cells against deleterious effects of high levels of intracellular glucose by downregulating the glucose transport system in the cells. In addition, it has been shown that 12-LO and 12-HETE support insulin-dependent glucose transporter-4 translocation to the plasma membrane by maintaining intact actin fiber network in the cardiomyocytes. Here we focus on the disparate cellular interactions by which 12-LO and 12-HETE affect the glucose transport system in vascular endothelial and smooth muscle cells and in cardiomyocytes.     

Functional annotation prediction: all for one and one for all

In an era of rapid genome sequencing and high-throughput technology, automatic function prediction for a novel sequence is of utter importance in bioinformatics. While automatic annotation methods based on local alignment searches can be simple and straightforward, they suffer from several drawbacks, including relatively low sensitivity and assignment of incorrect annotations that are not associated with the region of similarity. ProtoNet is a hierarchical organization of the protein sequences in the UniProt database. Although the hierarchy is constructed in an unsupervised automatic manner, it has been shown to be coherent with several biological data sources. We extend the ProtoNet system in order to assign functional annotations automatically. By leveraging on the scaffold of the hierarchical classification, the method is able to overcome some frequent annotation pitfalls.     

The binding of estrogen and estrogen antagonists to the estrogen receptor.

The model of the estrogen receptor as a dimer of identical, interacting subunits and data obtained by Sasson and Notides (1988, Mol. Endocrinol. 2, 307-312) were used to find the standard free energy changes that describe the binding of estradiol and 4-hydroxytamoxifen to the estrogen receptor. For the binding of estradiol or 4-hydroxytamoxifen to the estrogen receptor the data do not deviate systematically from the best fit to the model. The standard free energy change for binding of one molecule of estradiol at one site and one molecule of 4-hydroxytamoxifen at the second site of estrogen receptor indicates that 4-hydroxytamoxifen antagonizes the binding of estradiol to the estrogen receptor.     

Does the Functional Form of the Association Between Education and Mortality Differ by U.S. Region?

To understand the education–mortality association among U.S. adults, recent studies have documented its national functional form. However, the functional form of education–mortality relationship may vary across geographic contexts. The four U.S. Census regions differ considerably in their social and economic policies, employment opportunities, income levels, and other factors that may affect how education lowers the risk of mortality. Thus, we documented regional differences in the functional form of the education–mortality association and examined the role of employment and income in accounting for regional differences. We used data on non-Hispanic white adults (2,981,672, person years) aged 45–84 in the 2000–2009 National Health Interview Survey, with Linked Mortality File through 2011 (37,598 deaths) and estimated discrete-time hazard models. The functional form of education and adult mortality was best characterized by credentialism in the Midwest, Northeast, and for Western men. For Western women, the association was linear, consistent with the human capital model. In the South, we observed a combination of mechanisms, with mortality risk declining with each year of schooling and a step change with high school graduation, followed by steeper decline thereafter. Our work adds to the increasing body of research that stresses the importance of contexts in shaping the education–mortality relationship.     

Seasonal variation in hippocampal volume in a food-storing bird,the black-capped chickadee

Black-capped chickadees (Parus atricapillus) in upstate New York show a peak in food-hoarding intensity in October. We caught chickadees at six different times of the year and measured the volume of several brain structures. We found that the hippocampal formation, which is involved in spatial memory for cached food items, has a larger volume, relative to the rest of the brain, in October than at any other time of the year. We conclude that there is an association between the intensity of food hoarding and the volume of the hippocampal formation and suggest that the enhanced anatomy might be caused by the increased use of spatial memory. © 1995 John Wiley & Sons, Inc.     

Growth and bone mineralisation as affected by dietary calcium, phytic acid and vitamin D

1. Rats were fed various diets ranging from the normal chow, pure flour containing large amounts of phytic acid, Ca-enriched flour and mixtures of flour and normal food with various levels of calcium. 2. It was found that the animals eating the pure flour grew less and were smaller. 3. They suffered from hypocalcemia and had low plasma alkaline phosphatase and 25-HCC-vitamin D3 levels. 4. These animals had rib-cage deformities. 5. Additional calcium in the flour improved the animals' growth and calcification. 6. The mixed food did not greatly affect the animals and additional calcium did not improve growth or bone mineralisation. 7. The Bedouin eat large amounts of unleavened bread containing large amounts of phytates. 8. It is concluded that uptake of large amounts of phytates by the Bedouin eating unleavened bread is due to the flour and that the clinical manifestations are a direct result of the flour and not the lack of vitamin D due to covering the skin from sunlight.     

The effects of dimethylformamide on the interaction of the estrogen receptor with estradiol

The study of the mechanism of interaction of antiestrogens with the estrogen receptor is complicated by the limited solubility of these compounds and their nonspecific, hydrophobic interactions with proteins in estrogen receptor preparations and with the glass or plastic wall of the test tube. The organic solvent dimethylformamide increases the solubility of these compounds in aqueous solution and interferes with hydrophobic interactions with solid phases and thereby reduces their loss from the solution. For these reasons some investigators use dimethylformamide in the antiestrogen-estrogen receptor binding assay. In this study we report that dimethylformamide interferes with the estrogen receptor's binding kinetics and the estradiol-induced activation of the estrogen receptors, and inactivates the receptor.     

The oxidation of naphthalene sulfonate dyes by horse radish peroxidase

Horse radish peroxidase catalyses oxidation of ANS and TNS with hydrogen peroxide. TNS peroxidation may be followed fluorimetrically in the presence of as low as 10^?12m concentrations of the enzyme and permits determination of very low levels of peroxides. Initial rates of peroxidation of ANS and TNS confirmed the general mechanism of peroxidation by HRP. The second-order rate constants for the reduction of HRP compounds I and II were determined. Binding of the substrates to hydrophobic sites of bovine serum albumin or apoperoxidase rendered them inaccessible to the enzyme. While benzhydroxamic acid inhibited the oxidation of dianisidine, it exerted an activating effect on the peroxidation of naphthalene sulfonates. Due to the high reactivity of naphthalene sulfonates, their application as probes in biological systems containing possible traces of peroxidases and peroxides should be interpreted with great caution.