Mitochondrial membrane fatty acid composition in the marmoset monkey following dietary lipid supplementation

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflowerseed oil were fed to marmoset monkeys for 22 wk. The effect of such diets on plasma, red blood cell phospholipids, and liver, heart, kidney and brain mitochondrial phospholipid fatty acids was determined. Despite large differences in the level and type of lipid present in the experimental diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the membranes examined. The diets did, however, alter the proportion of the various classes of polyunsaturated fatty acids in the membrane phospholipids, with the sunflower-seed oil diet elevating and the sheep kidney fat diet reducing the n−6/n−3 unsaturated fatty acid ratio, relative to a low (mixed fat) reference diet. This change occurred in all membranes except brain, in which only a small response to altered dietary lipid intake was observed. Elevation of dietary linoleic acid led to an increase in membrane linoleic acid and a marked decrease in membrane arachidonic acid, such that the membranes from animals fed the sunflowerseed oil diet exhibited the lowest proportion of arachidonic acid. In this latter respect, the response of the marmoset monkey to dietary lipid supplementation differs markedly from the rat. Our inability to alter significantly membrane lipid saturation/unsaturation supports the notion that a homeostatic mechanism is in some way responsible for buffering membranes from the effects of significant changes in the nature of the dietary lipid intake.     

Influence of stimulants on electrodermal studies in Fragile X syndrome

Attention Deficit Hyperactivity Disorder (ADHD) is seen in the majority of children with Fragile X Syndrome (FraX). Previous work has documented an enhanced sweat response to stimuli in children with FraX compared to controls utilizing electrodermal response (EDR) measures. The present study assesses the EDRs both on and off stimulants in 19 children with ADHD and FraX compared to 17 age- and IQ-matched control patients with ADHD and developmental delays. Although the baseline EDRs were comparable between FraX patients and controls, the patients with FraX had a significant decrease in EDR amplitude and number of peaks when treated with stimulants compared to controls. This suggests that patients with FraX are more responsive to the enhancement of inhibitory systems that occur with stimulant use for ADHD. The use of a quantifiable measure, such as EDR, is recommended in future studies of treatment efficacy.     

The impact of rapid release cycles on the integration delay of fixed issues

The release frequency of software projects has increased in recent years. Adopters of so-called rapid releases—short release cycles, often on the order of weeks, days, or even hours—claim that they can deliver fixed issues (i.e., implemented bug fixes and new features) to users more quickly. However, there is little empirical evidence to support these claims. In fact, our prior work shows that code integration phases may introduce delays for rapidly releasing projects—98% of the fixed issues in the rapidly releasing Firefox project had their integration delayed by at least one release. To better understand the impact that rapid release cycles have on the integration delay of fixed issues, we perform a comparative study of traditional and rapid release cycles. Our comparative study has two parts: (i) a quantitative empirical analysis of 72,114 issue reports from the Firefox project, and a (ii) qualitative study involving 37 participants, who are contributors of the Firefox, Eclipse, and ArgoUML projects. Our study is divided into quantitative and qualitative analyses. Quantitative analyses reveal that, surprisingly, fixed issues take a median of 54% (57 days) longer to be integrated in rapid Firefox releases than the traditional ones. To investigate the factors that are related to integration delay in traditional and rapid release cycles, we train regression models that model whether a fixed issue will have its integration delayed or not. Our explanatory models achieve good discrimination (ROC areas of 0.80–0.84) and calibration scores (Brier scores of 0.05–0.16) for rapid and traditional releases. Our explanatory models indicate that (i) traditional releases prioritize the integration of backlog issues, while (ii) rapid releases prioritize issues that were fixed in the current release cycle. Complementary qualitative analyses reveal that participants’ perception about integration delay is tightly related to activities that involve decision making, risk management, and team collaboration. Moreover, the allure of shipping fixed issues faster is a main motivator for adopting rapid release cycles among participants (although this motivation is not supported by our quantitative analysis). Furthermore, to explain why traditional releases deliver fixed issues more quickly, our participants point out the rush for integration in traditional releases and the increased time that is invested on polishing issues in rapid releases. Our results suggest that rapid release cycles may not be a silver bullet for the rapid delivery of new content to users. Instead, our results suggest that the benefits of rapid releases are increased software stability and user feedback.     

Acyl-CoA Binding Protein Gene Ablation Induces Pre-implantation Embryonic Lethality in Mice

Unique among the intracellular lipid binding proteins, acyl-CoA binding protein (ACBP) exclusively binds long-chain fatty acyl-CoAs (LCFA-CoAs). To test if ACBP is an essential protein in mammals, the ACBP gene was ablated by homologous recombination in mice. While ACBP heterozygotes appeared phenotypically normal, intercrossing of the heterozygotes did not produce any live homozygous deficient (null) ACBP^(−/−) pups. Heterozygous and wild type embryos were detected at all post-implantation stages, but no homozygous ACBP-null embryos were obtained—suggesting that an embryonic lethality occurred at a pre-implantation stage of development, or that embryos never formed. While ACBP-null embryos were not detected at any blastocyst stage, ACBP-null embryos were detected at the morula (8-cell), cleavage (2-cell), and zygote (1-cell) pre-implantation stages. Two other LCFA-CoA binding proteins, sterol carrier protein-2 (SCP-2) and sterol carrier protein-x (SCP-x) were significantly upregulated at these stages. These findings demonstrate for the first time that ACBP is an essential protein required for embryonic development and its loss of function may be initially compensated by concomitant upregulation of two other LCFA-CoA binding proteins, but only at the earliest pre-implantation stages. The fact that ACBP is the first known intracellular lipid binding protein whose deletion results in embryonic lethality suggests its vital importance in mammals.     

Proteins that underlie neoplastic progression of ulcerative colitis

Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non‐dysplastic mucosa, we hypothesized that the same field defects will include abnormally expressed proteins. Here, we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared with (i) UC patients without dysplasia (non‐progressors), (ii) non‐dysplastic colonic tissue from UC patient with high‐grade dysplasia or cancer (progressors), (iii) high‐grade dysplastic tissue from UC progressors, and (iv) normal colon. We identified differential protein expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, and calcium‐binding proteins were some of the interesting classes of these proteins. Network analysis discovered that Sp1 and c‐myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over‐expressed proteins in the non‐dysplastic tissue of UC progressors, carbamoyl‐phosphate synthase 1 and S100P, were further confirmed by immunohistochemistry analysis. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non‐dysplastic mucosa that identify a patient's risk for UC dysplasia.     

Non‐natural Olefin Cyclopropanation Catalyzed by Diverse Cytochrome P450s and Other Hemoproteins

Recent work has shown that engineered variants of cytochrome P450_BM3 (CYP102A1) efficiently catalyze non‐natural reactions, including carbene and nitrene transfer reactions. Given the broad substrate range of natural P450 enzymes, we set out to explore if this diversity could be leveraged to generate a broad panel of new catalysts for olefin cyclopropanation (i.e., carbene transfer). Here, we took a step towards this goal by characterizing the carbene transfer activities of four new wild‐type P450s that have different native substrates. All four were active and exhibited a range of product selectivities in the model reaction: cyclopropanation of styrene by using ethyl diazoacetate (EDA). Previous work on P450_BM3 demonstrated that mutation of the axial coordinating cysteine, universally conserved among P450 enzymes, to a serine residue, increased activity for this non‐natural reaction. The equivalent mutation in the selected P450s was found to activate carbene transfer chemistry both in vitro and in vivo. Furthermore, serum albumins complexed with hemin were also found to be efficient in vitro cyclopropanation catalysts.     

The Relation Between Brain Activity During Memory Tasks and Years of Education in Young and Older Adults.

Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An experimental technique to measure the shunt resistance across a local region of a floating junction

The inclusion of a floating junction (FJ) at the surface of a solar cell is one way to obtain good-quality surface passivation. The development of FJ-passivated solar cells, however, has been hindered by the frequent occurrence of shunting across the FJ. Shunting can occur at specific regions of the FJ, such as at isolated points of the base contact or at the edges of the solar cell. This paper presents an experimental technique to determine the shunt resistance across local regions of an FJ, thereby providing a means to compare the prevalence of shunting in one region to another. By locating and quantifying the shunting in specific regions of an FJ, valuable insight into its cause can be obtained.     

A survey of graduate programs in electromagnetic applications

Survey results which summarize the research activities of 64 American colleges and universities in areas that deal with applications of electromagnetic theory are presented. The names and research interests of faculty at each institution are listed along with the numbers of MS and PhD students who are enrolled during March 1989 or graduated in 1988. The EM-related research funding and the average net annual compensation paid to graduate students are also given for the surveyed schools     

Regulation of polyunsaturated fatty acid metabolism in tissue phospholipids of obese (fa/fa) and lean (fa/−) Zucker rats. 1. Effect of dietary lipids on cardiac tissue

The present investigation addressed three questions: (i) Does the obese syndrome alter the fatty acid composition of cardiac tissue and membrane phospholipids in obese (fa/fa) rats? (ii) Are changes, if they occur, similar to those reported for tissues of the genetically obese (ob/ob) mouse? (iii) Can cardiac tissue phospholipids and their component fatty acids be modified by dietary lipids and if so does this occur to the same extent in both fa/fa and lean (Fa/?) rats? Proportions of polyunsaturated fatty acids (PUFA) in cardiac total phospholipids of fa/fa rats differed significantly from those of Fa/? rats and from those reported for ob/ob mice. Increased 18∶2n?6 and decreased 20∶4n?6 and 22∶6n?3 in fa/fa rats indicated impaired PUFA metabolism, possibly reduced Δ6 and/or Δ5 desaturase activity, compared with Fa/? rats. No differences in hepatic Δ6 and Δ5 desaturase activity between fa/fa and Fa/? were found but enhanced activity of Δ9 desaturase activity in fa/fa as compared to Fa/? was evident. Inclusion of sunflower oil (SO) or triolein (TO) at 5% and 20% by weight in the diet elicited marked changes in the fatty acyl composition of cardiac phospholipids in both fa/fa and Fa/? rats when compared with animals fed the control Oxoid diet alone. Supplementation with triolein was most effective, reducing 18∶2n?6 and increasing 20∶4n?6 proportions in fa/fa rats so that they resembled those in Fa/? rats fed the control Oxoid diet. The type of fat rather than the amount of its dietary intake appears to be the main determinant of the observed changes in phospholipid composition. Pair feeding hyperphagic fa/fa rats to the lower intakes of Fa/? rats did not abolish the characteristic differences in the proportions of PUFA in cardiac phospholipids between the two phenotypes. The effect of triolein on cardiac phospholipid fatty acid composition in the present studies is intriguing and may be relevant in understanding the beneficial role of dietary olive oil in ameliorating cardiovascular disease in man.