A model of the angiotensin AT 1 receptor and site-directed mutagenesis were used to identify key residues involved in ligand binding. We propose that substitution of these residues causes the loss of an interaction between transmembrane helices III and VII, which allows the AT 1 receptor to "relax" into its active conformation.The renin-angiotensin system plays a vital role in the regulation of cardiovascular function, and its activity may be abnormal in a number of disease states. The effector molecule of this system, the octapeptide angiotensin II (Ang II), 1 has a number of actions in a variety of cell types (1). Two distinct Ang II receptor subtypes, AT 1 and AT 2 have been identified (2). This characterization is based on the differential selectivity for these two receptors of the non-peptide Ang II receptor antagonists, DuP 753 (losartan; AT 1 selective) and PD123177 (AT 2 selective). In addition, the modified peptides CGP42112A (3) and [p-amino-Phe 6 ]angiotensin II (pNH 2 F 6 AII) (4), both display selectivity for the AT 2 receptor over the AT 1 receptor. Furthermore, several studies suggest that AT 1 and AT 2 receptors display subtle differences in their binding affinities for Ang II and angiotensin III (Ang III). AT 2 receptors bind Ang II and Ang III with equal affinity (5-8), while AT 1 receptors exhibit a slightly higher affinity for Ang II, between 3-and 20-fold greater than Ang III (9 -11). Many of the recognized actions of Ang II appear to be mediated through AT 1 receptors, predominantly through activation of the phospholipase C signal transduction pathway.AT 1 receptors have been cloned from a variety of species and tissues (9 -15). All these AT 1 receptors consist of a single polypeptide, 359 amino acids in length, arranged with a topography comprising seven ␣-helical transmembrane regions (TM I-VII), typical of the G-protein-coupled receptor family. They display a high degree of sequence identity at the amino acid level (over 94% identical between all mammalian species). Two closely related isoforms (AT 1A and AT 1B ) encoded by different genes have been identified in the rat and mouse (13, 16) Recently AT 2 receptors have been cloned (17-19), which are also members of the G-protein-coupled receptor family. They consist of 363 amino acids and share only 34% sequence identity at the amino acid level to the AT 1 receptors.Mutagenesis studies of the AT 1 receptor have recently identified residues important in the binding of the non-peptide antagonist, losartan, and the natural ligand Ang II. These residues appear to be mutually exclusive, since amino acid substitutions, which affect losartan binding, do not alter Ang II binding, and vice versa. The major determinants of losartan binding appear to be residues located within the transmembrane helices . In contrast, the major determinants of Ang II binding appear to be residues present in the extracellular regions, particularly in the N-terminal extension adjacent to the first transmembrane helix and in the C-terminal part of the third extracellula...

; Judith A Smith -j.a.smith@lancaster.ac.uk; Alison J Lee -a.j.lee@leeds.ac.uk; R Elwyn Isaac -r.e.isaac@leeds.ac.uk; Alan D Shirras* -a.shirras@lancaster.ac.uk * Corresponding author AbstractBackground: Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE), play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins is largely unknown. Sequencing of the A. gambiae genome has revealed a number of ACE-like genes but probable errors in the Ensembl annotation have left the number of ACE-like genes, and their structure, unclear.

Sucrose polyester (SPE) is a tasteless, odourless substance which reduces plasma cholesterol concentrations and may therefore be valuable as a fat substitute in human foodstuffs. It has recently been approved for use in snack foods by the United States Federal Drug Administration. The current study was designed to investigate its effects on gastrointestinal physiology and nutrient absorption in human subjects. A 6-month (2 × 3-month periods) double-blind, placebocontrolled, randomized, cross-over trial of SPE and control fat was performed in healthy freeliving volunteers. Subjects consumed 20-40 g of SPE daily (mean 26 . 8 (se 6 . 8) g) which reduced the intake of total and saturated fat but had no effect on energy intake or body weight. Plasma cholesterol and triacylglycerols were reduced. The frequency of bowel movements and their urgency were increased and anal leakage occured in 7 . 2 % of subjects. Abdominal pain was more frequent in subjects receiving SPE and was significantly greater than in the control group after 8 weeks feeding. The plasma concentrations of vitamin E and six carotenoids were significantly reduced. Routine haematology and biochemistry, other vitamins, intestinal biopsies, bile-salt retention, rectal prostaglandins, fractional Ca absorption and aminopyrine metabolism were unaffected. The ingestion of foods containing 20-40 g SPE daily provoked significant gastrointestinal problems. This intake is greater than that to be expected from the use of SPE in savoury snack foods, for which it has been approved by the United States Federal Drug Administration. However, the favourable effects on lipid profiles must be balanced against the reduction in the concentrations of vitamins and carotenoids, as these compounds may have beneficial effects on health through protection from free-radical oxidative stress. Sucrose polyester: Absorption: Cholesterol

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Obesity is a highly prevalent concern in American schoolchildren and is associated with a myriad of chronic health issues, such as type 2 diabetes, asthma, sleep problems, and premature mortality. Furthermore, obesity is associated with adverse psychological factors, including symptoms of depression, disordered eating, low self-esteem, poor quality of life, social isolation, and avoidance of healthcare services. It is therefore critical that school professionals understand the problem of childhood obesity as well as effective strategies for addressing the problem and its social impact. This chapter provides an overview of childhood overweight and obesity and the associated complications related to physical health, academic achievement. and peer interactions. It includes a review of considerations and strategies for school-based professionals to engage in both assessment and intervention to address childhood obesity in students.