6,983 research outputs found

    Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years

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    Objective: To examine whether dietary intake of specific flavonoid sub-classes is associated with weight change over time, including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers. Design: Three prospective cohort studies. Setting: Health professionals in the United States. Participants: 124,086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS), and Nurses’ Health Study II (NHS II). Main outcome measure: Self-reported change in weight over multiple 4-year time intervals between 1986 and 2011. Results: Increased consumption of most flavonoid sub-classes, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers was inversely associated with weight change over 4-year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (-0.22 lbs, 95% CI -0.30 to -0.15 lbs per additional SD/day, 10 mg), flavonoid polymers (-0.18 lbs, 95% CI -0.28 to -0.08 lbs per additional SD/day, 138 mg), and flavonols (-0.16 lbs, 95% CI -0.26 to -0.06 lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other sub-classes. Conclusions: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, may contribute to weight maintenance in adulthood, and may help to refine dietary recommendations for the prevention of obesity and its potential sequelae

    Adiposity and weight change in mid-life in relation to healthy survival after age 70 in women: prospective cohort study

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    Objective: To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages. Design: Prospective cohort study. Setting: The Nurses’ Health Study, United States. Participants: 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976). Main outcome measures: Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations. Results: Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P<0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight. Conclusions: These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood

    A Parameterised Complexity Analysis of Bi-level Optimisation with Evolutionary Algorithms

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    Bi-level optimisation problems have gained increasing interest in the field of combinatorial optimisation in recent years. In this paper, we analyse the runtime of some evolutionary algorithms for bi-level optimisation problems. We examine two NP-hard problems, the generalised minimum spanning tree problem and the generalised travelling salesperson problem in the context of parameterised complexity. For the generalised minimum spanning tree problem, we analyse the two approaches presented by Hu and Raidl (2012) with respect to the number of clusters that distinguish each other by the chosen representation of possible solutions. Our results show that a (1+1) evolutionary algorithm working with the spanning nodes representation is not a fixed-parameter evolutionary algorithm for the problem, whereas the problem can be solved in fixed-parameter time with the global structure representation. We present hard instances for each approach and show that the two approaches are highly complementary by proving that they solve each other’s hard instances very efficiently. For the generalised travelling salesperson problem, we analyse the problem with respect to the number of clusters in the problem instance. Our results show that a (1+1) evolutionary algorithm working with the global structure representation is a fixed-parameter evolutionary algorithm for the problem

    Lysyl-tRNA Synthetase from Pseudomonas aeruginosa: Characterization and Identification of Inhibitory Compounds

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    Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections and has highly developed systems for acquiring resistance against numerous antibiotics. The gene (lysS) encoding P. aeruginosa lysyl-tRNA synthetase (LysRS) was cloned and overexpressed, and the resulting protein was purified to 98% homogeneity. LysRS was kinetically evaluated, and the Km values for the interaction with lysine, adenosine triphosphate (ATP), and tRNALys were determined to be 45.5, 627, and 3.3 µM, respectively. The kcatobs values were calculated to be 13, 22.8, and 0.35 s−1, resulting in kcatobs/KM values of 0.29, 0.036, and 0.11 s−1µM−1, respectively. Using scintillation proximity assay technology, natural product and synthetic compound libraries were screened to identify inhibitors of function of the enzyme. Three compounds (BM01D09, BT06F11, and BT08F04) were identified with inhibitory activity against LysRS. The IC50 values were 17, 30, and 27 µM for each compound, respectively. The minimum inhibitory concentrations were determined against a panel of clinically important pathogens. All three compounds were observed to inhibit the growth of gram-positive organisms with a bacteriostatic mode of action. However, two compounds (BT06F11 and BT08F04) were bactericidal against cultures of gram-negative bacteria. When tested against human cell cultures, BT06F11 was not toxic at any concentration tested, and BM01D09 was toxic only at elevated levels. However, BT08F04 displayed a CC50 of 61 µg/mL. In studies of the mechanism of inhibition, BM01D09 inhibited LysRS activity by competing with ATP for binding, and BT08F04 was competitive with ATP and uncompetitive with the amino acid. BT06F11 inhibited LysRS activity by a mechanism other than substrate competition
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