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排序方式: 共有155条查询结果,搜索用时 7 毫秒
71.
Ohkanda J Lockman JW Yokoyama K Gelb MH Croft SL Kendrick H Harrell MI Feagin JE Blaskovich MA Sebti SM Hamilton AD 《Bioorganic & medicinal chemistry letters》2001,11(6):761-764
Malaria continues to represent a very serious health problem in the tropics. The current methods of clinical treatment are showing deficiencies due to the increased incidence of resistance in the parasite. In the present paper we report the design, synthesis, and evaluation of potential antimalarial agents against a novel target, protein farnesyltransferase. We show that the most potent compounds are active against Plasmodium falciparum in vitro at submicromolar concentrations. 相似文献
72.
A healthy lifestyle school-based obesity intervention was evaluated in a rural southern community where the rate of obesity ranks as the highest. School-age children (N = 450) ranging from 6 to 10 years of age (Mage = 8.34) participated in monthly physical activity and nutritional events during a 9-month academic year. The children's nutritional knowledge, number of different physical activities, fitness level, dietary habits, waist circumference, BMI percentile, and percentage body fat were measured pre- and postintervention. Changes on these measures were compared to students in a school employing the school system's standard health curriculum. Regression analyses with residualized change scores revealed that the intervention school showed statistically significant improvement in percentage body fat, physical activity, performance on fitness tests, and dietary habits compared to the control school. There was no evidence of differences in outcomes based on gender or ethnicity/race. With rates of obesity and overweight reaching 50% in southern rural communities, intervening early in development may offer the best outcome because of the difficulties with changing lifestyle behaviors later in adulthood. A population-based approach is recommended over a targeted approach to cultivate a culture of healthy lifestyle behaviors when children are developing their health-care habits. Evidence suggests that both boys and girls, and African-American and white children can benefit equally from such interventions. 相似文献
73.
Henagan TM Forney L Dietrich MA Harrell BR Stewart LK 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,113(3):393-400
The existing paradigm of exercise-induced decreases in chronic inflammation focuses on the expression of inflammatory receptors on systemic monocytes in response to exercise training, with the role of anti-inflammatory receptors largely ignored. Our recent preliminary studies indicate that the anti-inflammatory melanocortin receptors (MCRs) may play a role in modulating exercise-induced decreases in chronic inflammation. Here, we present a study designed to determine the effect of intense, resistance exercise training on systemic monocyte MCR expression. Because low-grade chronic inflammation is associated with elevated cardiometabolic risk in healthy populations and exercise decreases chronic inflammation, we investigated the associations between systemic monocyte cell surface expression of MCRs and inflammatory markers as a possible mechanism for the beneficial anti-inflammatory effects of resistance training. To this end, the present study includes 40 adults (aged 19-27 yr) and implements a 12-wk periodized, intensive resistance training intervention. Melanocortin 1 and 3 receptor expression on systemic monocytes and inflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, IL-1β, and IL-10, were measured before and after the intervention. Resistance training significantly altered MCR systemic monocyte cell surface expression, had no chronic effects on IL-6, IL-1β, or IL-10 expression, but significantly decreased CRP levels from a moderate to a low cardiovascular disease risk category. More specifically, decreased melanocortin 3 receptor expression significantly correlated with decreased CRP, independent of changes in adiposity. These data suggest that the observed responses in MCR expression and decreases in cardiovascular disease risk in response to resistance training represent an important anti-inflammatory mechanism in regulating exercise-induced decreases in chronic inflammation that occur independent of chronic changes in systemic cytokines. 相似文献
74.
Net CO(2) Assimilation Rate of Grapevine Leaves in Response to Trunk Girdling and Gibberellic Acid Application 下载免费PDF全文
Net CO2 assimilation rate (A), stomatal conductance (gs), and weight per unit leaf area (W) were determined on Thompson Seedless grapevines grown in the field. Treatments included fruit set applications of gibberellic acid (40 milligrams gibberellic acid (GA3) per liter) to vines, shoots and clusters, alone and in combination with trunk girdling. Leaf A and gs were measured prior to and 3, 6, and 13 days after fruit set. Weight per unit leaf area was determined on leaves collected subsequent to gas exchange measurements. Leaf A of girdled vines was reduced approximately 30% when compared to the control 13 days after treatment. The reduction in A due to girdling was not as great when vines were sprayed with GA3. GA3 sprays alone had no significant effect on A. Stomatal conductance was reduced by girdling 13 days after treatment. Weight per unit leaf area was 17% greater for trunk girdled vines when compared to the controls. Results indicate GA3 affected net CO2 assimilation rate only on girdled vines, a treatment which increased weight per unit leaf area. 相似文献
75.
A newly derived strain of Histoplasma capsulatum can be grown stably as yeast in a minimal medium containing glucose, biotin, tartrate and inorganic salts. 相似文献
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78.
William A. Harrell Rebecca C. Vieira Susan M. Ensel Vicki Montgomery Rebecca Guernieri Vanessa S. Eccard Yvette Campbell Virginia Roxas-Duncan John H. Cardellina Robert P. Webb Leonard A. Smith 《Bioorganic & medicinal chemistry letters》2017,27(3):675-678
Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ?1 μM and 11 effective at ?2 μM in an ex vivo assay. 相似文献
79.
80.
Rhoads JM Corl BA Harrell R Niu X Gatlin L Phillips O Blikslager A Moeser A Wu G Odle J 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(3):G913-G922
Recent identification of the mammalian target of rapamycin (mTOR) pathway as an amino acid-sensing mechanism that regulates protein synthesis led us to investigate its role in rotavirus diarrhea. We hypothesized that malnutrition would reduce the jejunal protein synthetic rate and mTOR signaling via its target, ribosomal p70 S6 kinase (p70(S6K)). Newborn piglets were artificially fed from birth and infected with porcine rotavirus on day 5 of life. Study groups included infected (fully fed and 50% protein calorie malnourished) and noninfected fully fed controls. Initially, in "worst-case scenario studies," malnourished infected piglets were killed on days 1, 3, 5, and 11 postinoculation, and jejunal samples were compared with controls to determine the time course of injury and p70(S6K) activation. Using a 2 x 2 factorial design, we subsequently determined if infection and/or malnutrition affected mTOR activation on day 3. Western blot analysis and immunohistochemistry were used to measure total and phosphorylated p70(S6K); [(3)H]phenylalanine incorporation was used to measure protein synthesis; and lactase specific activity and villus-crypt dimensions were used to quantify injury. At the peak of diarrhea, the in vitro jejunal protein synthetic rate increased twofold (compared with the rate in the uninfected pig jejunum), concomitant with increased jejunal p70(S6K) phosphorylation (4-fold) and an increased p70(S6K) level (3-fold, P < 0.05). Malnutrition did not alter the magnitude of p70(S6K) activation. Immunolocalization revealed that infection produced a major induction of cytoplasmic p70(S6K) and nuclear phospho-p70(S6K), mainly in the crypt. A downregulation of semitendinosus muscle p70(S6K) phosphorylation was seen at days 1-3 postinoculation. In conclusion, intestinal activation of p70(S6K) was not inhibited by malnutrition but was strongly activated during an active state of mucosal regeneration. 相似文献