DNA building blocks: keeping control of manufacture

Ribonucleotide reductase (RNR) is the only source for de novo production of the four deoxyribonucleoside triphosphate (dNTP) building blocks needed for DNA synthesis and repair. It is crucial that these dNTP pools are carefully balanced, since mutation rates increase when dNTP levels are either unbalanced or elevated. RNR is the major player in this homeostasis, and with its four different substrates, four different allosteric effectors and two different effector binding sites, it has one of the most sophisticated allosteric regulations known today. In the past few years, the structures of RNRs from several bacteria, yeast and man have been determined in the presence of allosteric effectors and substrates, revealing new information about the mechanisms behind the allosteric regulation. A common theme for all studied RNRs is a flexible loop that mediates modulatory effects from the allosteric specificity site (s-site) to the catalytic site for discrimination between the four substrates. Much less is known about the allosteric activity site (a-site), which functions as an on-off switch for the enzyme's overall activity by binding ATP (activator) or dATP (inhibitor). The two nucleotides induce formation of different enzyme oligomers, and a recent structure of a dATP-inhibited α6β2 complex from yeast suggested how its subunits interacted non-productively. Interestingly, the oligomers formed and the details of their allosteric regulation differ between eukaryotes and Escherichia coli Nevertheless, these differences serve a common purpose in an essential enzyme whose allosteric regulation might date back to the era when the molecular mechanisms behind the central dogma evolved

The College Health and Wellness Study: Baseline Correlates of Overweight among African Americans

Overweight and obesity are epidemic in the United States, particularly among minority populations. This epidemic contributes to the development of chronic conditions that occur later in life such as type 2 diabetes and hypertension. Therefore, it is important to identify factors associated with the development of obesity during young adulthood. We conducted a cross-sectional survey among students graduating from a Historically Black College or University (HBCU) in the Mid-Atlantic region. Participants were 392 predominantly African American seniors graduating in the spring of 2003. Data were collected using a self-administered paper and pencil questionnaire which focused on weight, weight management activities, individual and familial weight history, and health status indicators. Participants were on average 24 ± 5 years of age and 69% female; over 90% identified as African American or Black. According to NIH guidelines, about 30% of males and 28% of females were considered overweight, 12% of males and 7% of females were considered obese, and 7% of males and females were considered extremely obese. Significant correlates of being more overweight were being married, having children, lower socio-economic status, weight-loss attempts, personal and family history of overweight, and poorer health status. These data suggest that among this sample, the prevalence of overweight and obesity is similar to other populations of young African American adults. Familial factors such as socio-economic status and family weight history were important correlates of overweight. Overweight is a significant problem in this population, and these data should be useful for developing weight loss interventions aimed at young adults

Prepregnancy Obesity and Birth Outcomes

We investigate the association between prepregnancy obesity and birth outcomes using fixed effect models comparing siblings from the same mother. A total of 7,496 births to 3,990 mothers from the National Longitudinal Survey of Youth 1979 survey are examined. Outcomes include macrosomia, gestational length, incidence of low birthweight, preterm birth, large and small for gestational age (LGA, SGA), c-section, infant doctor visits, mother's and infant's days in hospital post-partum, whether the mother breastfed, and duration of breastfeeding. Association of income outcomes with maternal pre-pregnancy obesity was examined using Ordinary Least Squares (OLS) regression to compare across mothers and fixed effects to compare within families. In fixed effect models we find no statistically significant association between most outcomes and prepregnancy obesity with the exception of LGA, SGA, low birth weight and preterm birth. We find that prepregnancy obesity is associated with a with lower risk of low birthweight, SGA, and preterm birth but controlling for prepregnancy obesity, increases in GWG lead to increased risk of LGA. Contrary to previous studies, which have found that maternal obesity increases the risk of c-section, macrosomia and LGA, while decreasing the probability of breastfeeding, our sibling comparison models reveal no such association. In fact, our results suggest a protective effect of obesity in that women who are obese prepregnancy have longer gestation lengths, and are less likely to give birth to a preterm or low birthweight infant