Abstract-We previously reported the identification of a locus on mouse chromosome 6 that confers almost total resistance to atherogenesis, even on a hypercholesterolemic (LDL receptor-null) background. 5-Lipoxygenase (5-LO) is the rate-limiting enzyme in leukotriene synthesis and was among the chromosome 6 locus candidate genes that we examined. The levels of 5-LO mRNA were reduced about 5-fold in a congenic strain, designated CON6, containing the resistant chromosome 6 region derived from the CAST/Ei strain (CAST), as compared with the background C57BL/6J (B6) strain. 5-LO protein levels were similarly reduced in the CON6 mice. Sequencing of the 5-LO cDNA revealed several differences between CON6 and the B6 strain. To test the whether 5-LO is responsible for the resistant phenotype, we bred a 5-LO knockout allele onto an LDL receptor-null (LDLR Ϫ/Ϫ ) background. On this background, the mice bred poorly and only heterozygous 5-LO knockout mice were obtained. These mice showed a dramatic decrease (Ͼ26-fold; PϽ0.0005) in aortic lesion development, similar to the CON6 mice. Immunohistochemistry revealed that 5-LO was abundantly expressed in atherosclerotic lesions of apoE Ϫ/Ϫ and LDLR Ϫ/Ϫ deficient mice, appearing to colocalize with a subset of macrophages but not with all macrophage-staining regions. When bone marrow from 5-LO ϩ/Ϫ mice was transplanted into LDLR Ϫ/Ϫ , there was a significant reduction in atherogenesis, suggesting that macrophage 5-LO is responsible, at least in part, for the effect on atherosclerosis. These results indicate that 5-LO contributes importantly to the atherogenic process and they provide strong presumptive evidence that reduced 5-LO expression is partly responsible for the resistance to atherosclerosis in CON6 mice. This signals a cascade of leukocyte recruitment, further lipoprotein oxidation, foam cell formation, necrosis, and fibroproliferation. To identify genes that contribute to this complex process, we previously constructed a cross between an atherosclerosis-resistant mouse strain, CAST, and a susceptible strain, B6. A major locus for atherosclerosis was identified on mouse chromosome 6 and was subsequently confirmed with the congenic strain designated CON6 in which the central region of chromosome 6 from CAST was bred onto a B6 background. 3 These CON6 mice had reduced insulin levels and dramatically decreased lesion formation when bred onto an LDL receptornull (LDLR Ϫ/Ϫ ) background and fed an atherogenic diet. Moreover, bone marrow transplantation studies indicated that the resistant phenotype was conferred in part by bone marrowderived cells.In examining the congenic region for potential positional candidate genes, we observed that 5-lipoxygenase (5-LO) mapped directly underneath the linkage peak for the locus. 5-LO is the rate-limiting enzyme in leukotriene (LT) biosynthesis 4 and is expressed primarily in leukocytes, including monocytes and macrophages. 5 Leukotrienes are potent proinflammatory lipid mediators derived from arachidonic acid and have been shown to affect s...

The herbicide glyphosate is effectively detoxified by N-acetylation. We screened a collection of microbial isolates and discovered enzymes exhibiting glyphosate N-acetyltransferase (GAT) activity. Kinetic properties of the discovered enzymes were insufficient to confer glyphosate tolerance to transgenic organisms. Eleven iterations of DNA shuffling improved enzyme efficiency by nearly four orders of magnitude from 0.87 mM-1 min-1 to 8320 mM-1 min-1. From the fifth iteration and beyond, GAT enzymes conferred increasing glyphosate tolerance to Escherichia coli, Arabidopsis, tobacco, and maize. Glyphosate acetylation provides an alternative strategy for supporting glyphosate use on crops.

Abstract-Heme oxygenase (HO-1) is the rate-limiting enzyme in the catabolism of heme, which leads to the generation of biliverdin, iron, and carbon monoxide. It has been shown to have important antioxidant and antiinflammatory properties that result in a vascular antiatherogenic effect. To determine whether HO-1 expression in macrophages constitutes a significant component of the protective role in atherosclerosis, we evaluated the effect of decreased or absent HO-1 expression in peritoneal macrophages on oxidative stress and inflammation in vitro, and the effect of complete deficiency of HO-1 expression in macrophages in atherosclerotic lesion formation in vivo. We found that compared with HO-1 ϩ/ϩ controls, peritoneal macrophages from HO-1 Ϫ/Ϫ and HO-1 ϩ/Ϫ mice exhibited (1) increased reactive oxygen species (ROS) generation, (2) increased proinflammatory cytokines such as monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), and (3) increased foam cell formation when treated with oxLDL, attributable in part to increased expression of scavenger receptor A (SR-A). Bone marrow transplantation experiments performed in lethally irradiated LDL-R null female mice, reconstituted with bone marrow from HO-1 Ϫ/Ϫ versus HO-1 ϩ/ϩ mice, revealed that HO-1 Ϫ/Ϫ reconstituted animals exhibited atherosclerotic lesions with a greater macrophage content as evaluated by immunohistochemistry and planimetric assessment. We conclude that HO-1 expression in macrophages constitutes an important component of the antiatherogenic effect by increasing antioxidant protection and decreasing the inflammatory component of atherosclerotic lesions.

Motivated employees play a key role in organization success, and past research indicates a positive association between perceptions of empowerment and motivation. A prominent model put forth by Spreitzer (1995) suggests that two major components of control systems will positively affect employee feelings of empowerment—performance feedback and performance-based reward systems. This experimental study contributes to the behavioral accounting literature by examining how specific types of performance feedback and performance-based rewards affect three psychological dimensions of empowerment. Also, we use a relatively simple context to investigate whether predictions validated on surveys of managers also hold for lower-level workers. Our results suggest that feedback and rewards affect the dimensions of empowerment differently for lower-level workers than they do for managers. Namely, performance feedback was positively associated with only one dimension and performance-based rewards had negative effects on two out of the three dimensions. In addition, overall motivation was not significantly associated with two of the three empowerment dimensions. Implications of this study are that techniques that work to increase manager perceptions of empowerment may not work at lower organizational levels and, even if successful, the related increase in employee motivation may not be significant.

A unique transfer RNA has been identified in human and bovine mitochondria that lacks the "dihydrouridine" loop and stem structure. This tRNA is mitochondrially coded as shown by DNA sequence analysis of the human and bovine mitochondrial DNA. Sequence analysis of the RNA shows that it is post-transcriptionally modified by the addition of CCA at the 3' terminus and that at least one base is modified. As predicted by its anticodon (GCU, corresponding to the serine codons AGU/C) this tRNA can be aminoacylated with serine when purified mitochondria are incubated in a medium containing 3H-serine.

The complete nucleotide sequence of Helicoverpa zea single-nucleocapsid nucleopolyhedrovirus (HzSNPV) has been determined (130869 bp) and compared to the nucleotide sequence of Helicoverpa armigera (Ha) SNPV. These two genomes are very similar in their nucleotide (97% identity) and amino acid (99% identity) sequences. The coding regions are much more conserved than the non-coding regions. In HzSNPV/HaSNPV, the 63 open reading frames (ORFs) present in all baculoviruses sequenced so far are much more conserved than other ORFs. HzSNPV has four additional small ORFs compared with HaSNPV, one of these (Hz42) being in a correct transcriptional context. The major differences between HzSNPV and HaSNPV are found in the sequence and organization of the homologous regions (hrs) and the baculovirus repeat ORFs (bro genes). The sequence identity between the HzSNPV and HaSNPV hrs ranges from 90% (hr1) to almost 100% (hr5) and the hrs differ in the presence/absence of one or more type A and/or B repeats. The three HzSNPV bro genes differ significantly from those in HaSNPV and may have been acquired independently in the ancestral past. The sequence data suggest strongly that HzSNPV and HaSNPV are variants of the same virus species, a conclusion that is supported by the physical and biological data.

Abstract-The genes contributing to the common forms of atherosclerosis are largely unknown. One approach to dissecting complex traits such as atherosclerosis is to use animal models, such as the mouse, to map and characterize the genetic loci involved. We now report the identification of a locus for aortic lesion formation on mouse chromosome 6 that exhibits a highly significant lod score of 6.7 in a genetic cross between the susceptible strain, C57BL/6J, and the resistant strain, CAST/Ei. The locus was confirmed by constructing a congenic strain in which the chromosome 6 segment from CAST/Ei was transferred to a C57BL/6J background in a series of backcrosses. The congenic strain was almost completely resistant to diet-induced atherosclerosis. The chromosome 6 segment was also transferred onto the background of an LDL receptor-null mutation and resulted again in almost complete resistance to aortic lesion formation. This locus also influenced insulin levels but did not affect plasma lipoprotein levels, blood pressure, or body fat. The chromosome 6 gene, which we call Artles (for arterial lesions), did not affect endothelial cell responses to oxidized LDL, but lesion formation was partially reduced through bone marrow transplantation. The locus contains the candidate gene peroxisome proliferator-activated receptor-␥, and the congenic mice exhibited significantly reduced expression of peroxisome proliferator-activated receptor-␥. A therosclerosis is a disease of the large arteries that is the primary cause of heart disease and stroke. A large number of risk factors for the disease have been identified through epidemiological studies, including genetic traits, such as elevated cholesterol, elevated blood pressure, reduced HDL levels, and male sex, as well as environmental factors, such as smoking and a high-fat diet. Altogether, these risk factors do not appear to fully explain atherosclerosis. The search for genes contributing to the common multifactorial forms of atherosclerosis has been only modestly successful, with a major problem being the very complex etiology of the disease. 1 One potentially powerful approach to understanding the genetic factors in the disease is the analysis of animal models such as mice. Inbred strains of mice differ greatly in susceptibility to the development of atherosclerotic lesions when maintained on high-fat diets; they also differ regarding the background of hyperlipidemia-inducing null mutations of apolipoprotein E or the LDL receptor (LDLR). [2][3][4][5][6][7] We now report the mapping and partial characterization of a genetic locus on chromosome 6 that blocks the development of both early and advanced atherosclerotic lesions. A congenic strain carrying the locus exhibited little or no lesion formation even under conditions of extreme hyperlipidemia resulting from an LDLR mutation. The locus did not affect several risk factors normally associated with atherosclerosis, including LDL and VLDL levels, HDL levels, and blood pressure, suggesting the involvement of a novel pathway fo...

A growing body of literature related to continuous auditing topics has developed. Advances in information technology and web-based applications are making monitoring and control of operations through continuous auditing increasingly important. The objective of this paper is to describe, summarize, and provide a framework for classifying the contributions of the diverse literature addressing the topic of continuous auditing. This paper was intended to provide researchers and practitioners with a background in continuous auditing topics. Our broad view of the literature is also designed to discover areas holding the potential for future research. Research streams are divided into five major categories: demand factors, theory and guidance, enabling technologies, applications, and impacts. Over 80 papers have been identified that relate to these areas. Many more articles exist, especially in the area of enabling technologies. However, the focus of our paper is the literature most closely related to continuous auditing.