Epidemiological surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein AI (ApoA-I), the major protein component of HDL, and the risk for atherosclerosis in humans. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions.

End-to-end fusion of critically shortened telomeres in higher eucaryotes is presumed to be mediated by nonhomologous end-joining (NHEJ). Here we describe two PCR-based methods to monitor telomere length and examine the fate of dysfunctional telomeres in Arabidopsis lacking the catalytic subunit of telomerase (TERT) and the DNA repair proteins Ku70 and Mre11. Primer extension telomere repeat amplification relies on the presence of an intact G-overhang, and thus measures functional telomere length. The minimum functional telomere length detected was 300–400 bp. PCR amplification and sequence analysis of chromosome fusion junctions revealed exonucleolytic digestion of dysfunctional ends prior to fusion. In ku70 tert mutants, there was a greater incidence of microhomology at the fusion junction than in tert mutants. In triple ku70 tert mre11 mutants, chromosome fusions were still detected, but microhomology at the junction was no longer favored. These data indicate that both Ku70 and Mre11 contribute to fusion of critically shortened telomeres in higher eucaryotes. Furthermore, Arabidopsis processes critically shortened telomeres as double-strand breaks, using a variety of end-joining pathways

CHAN, CATHERINE B., ELIZABETH SPANGLER, JAMES VALCOUR, AND CATRINE TUDOR-LOCKE.Cross-sectional relationship of pedometer-determined ambulatory activity to indicators of health. Obes Res. 2003; 11:1563-1570. Objective: To describe the cross-sectional relationship between an objective measure of walking (pedometer-determined steps/day) and general indicators of health, a prior diagnosis of one or more components of the metabolic syndrome, and self-reported occupational activity in a generally sedentary working population. Research Methods and Procedures:Steps/day were compared with previous diagnosis of one or more components of the metabolic syndrome (by self-administered questionnaire) and with general health indicators including BMI, waist circumference, resting heart rate, and blood pressure in 182 subjects in Prince Edward Island, Canada. Study participants were volunteer employees recruited from five workplaces where, in general, the job types were moderately or highly sedentary. Results: Steps/day were 7230 Ϯ SD 3447 for women (n ϭ 153) and 8265 Ϯ 2849 (n ϭ 21) for men. Pedometerdetermined steps/day were associated inversely with BMI (r ϭ Ϫ0.4005, p Ͻ 0.0001) in all participants and waist circumference in females only (r ϭ Ϫ0.4303, p Ͻ 0.0001). There was a low correlation between steps/day and diastolic blood pressure in the whole sample (r ϭ Ϫ0.2140, p ϭ 0.0383). Participants who reported a prior diagnosis of one or more components of the metabolic syndrome (hypertension, hypercholesterolemia, heart disease, or type 2 diabetes) took fewer steps/day than healthy participants (p ϭ 0.0254). Pedometer-determined steps/day were positively associated with self-reported occupational activity (p ϭ 0.0002). Discussion: Fewer steps/day are associated with increased BMI, waist circumference, diastolic blood pressure, and components of the metabolic syndrome. Low occupational activity is a contributing factor to low total ambulatory activity.

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