Molecular evolution and balancing selection in the flavin-containing monooxygenase 3 gene (FMO3)

OBJECTIVES: Flavin-containing monooxygenase 3 (FMO3) is involved in the metabolism of foreign chemicals, including therapeutic drugs, and thus mediates interactions between humans and their chemical environment. Loss-of-function mutations in the gene cause the inherited disorder trimethylaminuria, or fish-odour syndrome. The objective was to gain insights into the evolutionary history of FMO3. METHODS: Genetic diversity within FMO3 was characterized by sequencing 6.3 kb of genomic DNA, encompassing the entire coding sequence, some intronic and 3'-untranslated region, and 3.4 kb of 5'-flanking sequence, in 23 potential trimethylaminuric Japanese, and the same 3.4 kb 5'-flanking region in 45 unaffected Japanese. Mutational relationships among haplotypes were inferred from a reduced-median network. The time depth of the variation and ages of individual mutations were estimated by maximum-likelihood coalescent analysis. Test statistics were used to investigate whether the variation is compatible with neutral evolution. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified, which segregated as seven distinct haplotypes. Estimated ages of the mutations indicate that almost all predated migration out of Africa. Analysis of the heterozygosity of FMO3 SNPs indicates that genetic differentiation among continental populations is low (FST=0.050). Test statistics, based on allele-frequency spectrum, number and diversity of haplotypes, linkage disequilibrium and interspecific sequence comparisons, showed a significant departure from neutral expectations, because of an excess of intermediate-frequency SNPs and haplotypes, a ragged pairwise mismatch distribution and an excess of replacement polymorphisms. CONCLUSION: The results provide evidence that FMO3 has been the subject of balancing selection. Finally, we identify mutations that are potential targets for selection.     

Relationship of bone health to yearlong physical activity in older Japanese adults: cross-sectional data from the Nakanojo Study

Introduction We determined associations between bone health and the quantity and quality of habitual physical activity in a cohort of 172 free-living Japanese aged 65–83 years (76 men, 96 women). Methods The number of steps taken and the intensity of physical activity were measured every 4 s throughout each 24-h period for 1 year, using a specially adapted accelerometer that distinguished up to 11 levels of physical activity (expressed in metabolic equivalents, METs). At the end of the year, a quantitative ultrasonic technique assessed each participant’s osteosonic index (OSI, reflecting bone stiffness in the calcaneus). Results The data were significantly described by linear and exponential regression models which showed that in both sexes the OSI score increased with increasing daily physical activity, up to the observed maximum values of approximately 14,000 steps/day and 50 min/day at an intensity >3 METs. However, when data were categorized into quartiles of physical activity, OSI scores were not significantly greater in persons exceeding recommended minimum standards of habitual physical activity (corresponding to counts of around 6,900 and 6,800 steps/day and durations >3 METs of around 18 and 16 min/day in men and women, respectively). All who met such criteria (with the exception of a few women) had OSI scores above the threshold for a clinical diagnosis of osteoporosis. Multivariate-adjusted logistic regression analyses predicted that men and especially women who engaged in <6,800 steps/day and <16 min/day of moderate-intensity physical activity were, respectively, 4.9–8.4 and 2.2–3.5 times more likely to sustain fractures than those participating in >8,200 steps/day and >25 min/day of activity >3 METs. Conclusion Causation cannot be inferred from a cross-sectional study. Nevertheless, we suggest that from the viewpoint of bone health, elderly people should be encouraged to engage in low- and moderate-intensity habitual physical activity, taking >7,000 steps/day with a duration >15 min/day at >3 METs.     

A comparison of the perceived and the ECG measured heart rate during cycle ergometer, treadmill and stairmill exercise before and after perceived heart rate training.

The ability to perceive exercise heart rate before and after training was tested in six young male university students, perceptions of heart rate being compared with ECG monitored heart rates during cycle ergometry, treadmill running and stairmill climbing. Between initial and final tests, subjects undertook 13 weeks of running training (2 h/day, 3-4 days/week), and during this period they compared their perceptions of heart rate with values observed on watch-type wrist-mounted pulse monitors. Individual initial perceptions showed only a moderate correlation with ECG values. This correspondence was improved as perceptions were compared with measured heart rates over the course of training, significantly so for the mode of exercise most similar to that adopted in the training sessions (treadmill running at a heart rate of 140 beats/min). The final accuracy of perceptions at a heart rate of 140 beats/min (error 8-9 beats/min during treadmill running) compared favourably with the accuracy of either pulse counting or the traditional rating of perceived exertion as commonly observed in the exercising public. This suggests that there may be an application for perceived heart rates in regulating the intensity of prescribed exercise.     

Research that informs Canada's physical activity guides: an introduction

The Canadian Society for Exercise Physiology (CSEP), in partnership with Health Canada and others, released Canada's first physical activity guide for adults in 1998, with specific versions for older adults in 1999 and for children and youth in 2002. Research in the physical activity sciences (e.g., basic science, behavioural assessment, dose-response relationships, epidemiology, health messaging, physical activity measurement) has advanced rapidly since these publications. A detailed review of relevant current research is thus required, to assess whether the existing guidelines and resulting guides need revision or renewal. This introductory paper provides a brief chronology of events leading to the preparation of this journal supplement, including a statement of purpose and an overview of organization and content. A brief discussion of the purpose of the physical activity guidelines and guides, intended biological, psychological, and behavioural outcomes, and the way in which guidelines relate to on-going measurement and surveillance is provided as a context for the papers that follow.