SVEP1 influences monocyte to macrophage differentiation via integrin α4ß1/α9ß1 and Rho/Rac signalling.

BACKGROUND: The large extracellular matrix protein SVEP1 mediates cell adhesion via integrin α9ß1. Recent studies have identified an association between a missense variant in SVEP1 and increased risk of coronary artery disease (CAD) in humans and in mice Svep1 deficiency alters the development of atherosclerotic plaques. However how SVEP1 functionally contributes to CAD pathogenesis is not fully understood. Monocyte recruitment and differentiation to macrophages is a key step in the development of atherosclerosis. Here, we investigated the requirement for SVEP1 in this process. METHODS: SVEP1 expression was measured during monocyte-macrophage differentiation in primary monocytes and THP-1 human monocytic cells. SVEP1 knockout THP-1 cell lines and the dual integrin α4ß1/α9ß1 inhibitor, BOP, were utilised to investigate the effect of these proteins in THP-1 cell adhesion, migration and cell spreading assays. Subsequent activation of downstream integrin signalling intermediaries was quantified by western blotting. RESULTS: SVEP1 gene expression increases in monocyte to macrophage differentiation in human primary monocytes and THP-1 cells. Using two SVEP1 knockout THP-1 cells we observed reduction in monocyte adhesion, migration, and cell spreading compared to control cells. Similar results were found with integrin α4ß1/α9ß1 inhibition. We demonstrate reduced activity of Rho and Rac1 in SVEP1 knockout THP-1 cells. CONCLUSIONS: SVEP1 regulates monocyte recruitment and differentiation phenotypes through an integrin α4ß1/α9ß1 dependent mechanism. GENERAL SIGNIFICANCE: These results describe a novel role for SVEP1 in monocyte behaviour relevant to CAD pathophysiology.

Kindergarten students' food preferences are not consistent with their knowledge of the Dietary Guidelines.

OBJECTIVES: To evaluate kindergarten students' understanding of the concepts and terminology in the Dietary Guidelines for Americans; to determine whether kindergarteners could name food sources of fat, salt, and sugar; and to find out how well they understood the relationship between diet, exercise, body fat, and health. Additionally, food preference information was collected so that kindergarteners' knowledge about the Dietary Guidelines could be compared with their food choices. DESIGN AND SUBJECTS: Focus-group interviews were conducted in two elementary schools with 12 groups of about five students each (n = 62). Four classrooms were self-selected depending on the teacher's willingness to facilitate student participation; the sample was not random. RESULTS: Students understood the general relationship between food choices, exercise, body fat, and health. They were able to name foods high in salt, fat, and sugar and thought consumption of sugary or fatty foods should be limited. Nevertheless, their food preferences were not consistent with recommendations of the Dietary Guidelines to moderate foods high in these nutrients. APPLICATIONS: Nutrition educators should be aware that young children might not understand terms frequently used such as animal sources of foods or variety. Students know what to eat, but their practices are inconsistent with their knowledge. Providing information about what to do is not enough. To help students transfer factual information to personal dietary practices, nutrition educators need to teach them how to apply the Dietary Guidelines within their food environment while maintaining acceptability in regard to taste.

Nutrition education needs and learning preferences of Michigan students in grades 5, 8, and 11.

An assessment of nutrition education needs and learning preferences of students in grades 5, 8, and 11 was conducted to target instruction toward areas of highest need and strongest interest of students using teaching methods they prefer. This research evaluated students' knowledge, attitudes, and practices related to the Dietary Guidelines for Americans, including knowledge of the new Food Guide Pyramid; attitudes about school lunches and learning about nutrition; nutrition topics of interest; and preferred methods for learning about nutrition. Although results varied across grade level, generally students need to learn about the Food Guide Pyramid; the relationship between dietary fat, weight status, and health; and food sources of fat, salt, and fiber. They want to learn about personal health--how to control weight, improve diet, and prevent disease--using instructional methods that actively involve them. Results provide information relative to students' interest, understanding, and application of the Dietary Guidelines.

Effect of nicotinamide on drug metabolizing enzymes in the neonatal rat.

Sprague-Dawley rats were raised by dams (mother reared, MR) or artificially reared from day 4 to day 11, using chronic intragastric cannulas, and infused with one of four diets: control (AR); or supplemented with nicotinamide-low (LN, 300 mg/l), medium (MN, 750 mg/l), or high (HN, 1500 mg/l). Liver to body weight ratios were higher in all artificially reared groups (AR, LN, MN, HN) compared to MR pups. The amount of recovered hepatic microsomal protein was lower in all artificially reared groups when compared with MR pups. Uridine diphosphoglucuronyl transferase activity with para-nitrophenol as the substrate (UDPGT-PNP) was greater in all of the artificially reared groups compared to the MR group. UDPGT-PNP activity in the HN group was greater than in the AR, LN, or MN groups. Cytochrome P-450 concentration was highest in the MR group, whereas there were no differences among the artificially reared groups. It was concluded that the artificial rearing process stimulated hepatic UDPGT-PNP activity and depressed cytochrome P-450 concentrations, whereas dietary supplementation with nicotinamide during the preweanling period resulted in a further increase in UDPGT-PNP activity.