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Search Results: 1 - 10 of 297599 matches for " J. Kelsey "
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Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins
Kelsey J Metzger, Michael A Thomas
BMC Evolutionary Biology , 2010, DOI: 10.1186/1471-2148-10-139
Abstract: In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events.Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML) were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR) gene family. The results of neutral vs. adaptive evolution (positive selection) hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω) >1.Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive selection code for amino acid residues located in extracellular domains of the receptor protein products.These results suggest that amino acid residues present in intracellular and membrane-bound domains are more selectively constrained for functional signal transduction and homo- or heterodimerization, whereas amino acid residues in extracellular domains of these receptor proteins evolve more quickly, perhaps due to heightened selective pressure resulting from ligand-binding and pathogen interactions of extracellular domains.Chemotactic or chemoattractant cytokine (chemokine) proteins are a unique division of cytokines characterized by
Correspondence of perceived vs. objective proximity to parks and their relationship to park-based physical activity
Kelsey J Lackey, Andrew T Kaczynski
International Journal of Behavioral Nutrition and Physical Activity , 2009, DOI: 10.1186/1479-5868-6-53
Abstract: We used data from 574 respondents who reported the distance to their closest park and compared this with objective measurements of proximity to the closest park. Both indicators were dichotomized as having or not having a park within 750 m. Audits of all park features within this distance were also conducted and other personal characteristics and neighborhood context variables (safety, connectedness, aesthetics) were gleaned from participants' survey responses. Participants also completed detailed seven-day PA log booklets from which measures of neighborhood-based and park-based PA were derived.Agreement was poor in that only 18% of respondents achieved a match between perceived and objective proximity to the closest park (kappa = 0.01). Agreement was higher among certain subgroups, especially those who reported engaging in at least some park-based PA. As well, respondents with a greater number of parks nearby, whose closest park had more features, and whose closest park contained a playground or wooded area were more likely to achieve a match. Having a ball diamond or soccer field in the closest park was negatively related to achieving a match between perceived and objective proximity. Finally, engaging in at least some park-based PA was not related to either perceived or objective proximity to a park, but was more likely when a match between and perceived and objective proximity occurred.Poor levels of correspondence were observed between self-reported and objective proximity to parks, but certain individual, neighborhood, and park variables increased the likelihood of a participant being aware of local parks. Future research should examine how people conceptualize parks and what urban and park planners can do to increase awareness and use of these community assets.Physical activity (PA) is important for health and a growing body of evidence points to the influence of neighborhood and community environments on population-level rates of activity and inactivity [1-3
Tetra-tert-butyl 13,14-dioxapentacyclo[,7.02,9.03,8]tetradeca-5,11-diene-5,6,11,12-tetracarboxylate
Alan J. Lough,Kelsey Jack,William Tam
Acta Crystallographica Section E , 2012, DOI: 10.1107/s1600536812039220
Abstract: The stereochemistry of the title compound, C32H44O10, at the cyclobutane ring is cis-anti-cis. The molecule lies across an inversion center. In the crystal, weak C—H...O hydrogen bonds connect molecules into chains along [100], forming R22(6) rings.
Tetramethyl 1,4-dimethyl-13,14-dioxapentacyclo[,7.02,9.03,8]tetradeca-5,11-diene-5,6,11,12-tetracarboxylate
Alan J. Lough,Kelsey Jack,William Tam
Acta Crystallographica Section E , 2012, DOI: 10.1107/s1600536812039219
Abstract: In the title compound, C22H24O14, the relative stereochemistry at the cyclobutane ring is cis-anti-cis and the methyl groups in the bicyclic rings are syn to each other. The two carboxylate groups attached to the same —C=C— bond are disordered over two sets of sites in a 0.603 (2):0.397 (2) ratio. In the crystal, weak C—H...O hydrogen bonds connect molecules into C(12) chains along [001] incorporating R222(10) rings.
Hexamethyl 13,14-dioxapentacyclo[,7.02,9.03,8]tetradeca-5,11-diene-1,4,5,6,11,12-hexacarboxylate
Alan J. Lough,Kelsey Jack,William Tam
Acta Crystallographica Section E , 2012, DOI: 10.1107/s1600536812039232
Abstract: In the title compound, C24H24O14, the stereochemistry at the cyclobutane ring is cis-anti-cis and the –COOMe groups in the bicyclic rings are syn to each other. The molecule lies on a twofold rotation axis. In the crystal, weak C—H...O hydrogen bonds connect molecules into chains along [001], forming R22(10) rings.
Cost and Emissions Implications of Coupling Wind and Solar Power  [PDF]
Seth Blumsack, Kelsey Richardson
Smart Grid and Renewable Energy (SGRE) , 2012, DOI: 10.4236/sgre.2012.34041
Abstract: We assess the implications on long-run average energy production costs and emissions of CO2 and some criteria pollutants from coupling wind, solar and natural gas generation sources. We utilize five-minute meteorological data from a US location that has been estimated to have both high-quality wind and solar resources, to simulate production of a coupled generation system that produces a constant amount of electric energy. The natural gas turbine is utilized to provide fill-in energy for the coupled wind/solar system, and is compared to a base case where the gas turbine produces a constant power output. We assess the impacts on variability of coupled wind and solar over multiple time scales, and compare this variability with regional demand in a nearby load center, and find that coupling wind and solar does decrease variability of output. The cost analysis found that wind energy with gas back-up has a lower levelized cost of energy than using gas energy alone, resulting in production savings. Adding solar energy to the coupled system increases levelized cost of energy production; this cost is not made up by any reductions in emissions costs.
Systemic Oxidative Stress Is Increased to a Greater Degree in Young, Obese Women Following Consumption of a High Fat Meal
Richard J. Bloomer,Kelsey H. Fisher-Wellman
Oxidative Medicine and Cellular Longevity , 2009, DOI: 10.4161/oxim.2.1.7860
Abstract: High fat meals induce oxidative stress, which is associated with the pathogenesis of disease. Obese individuals have elevated resting biomarkers of oxidative stress compared to non-obese. We compared blood oxidative stress biomarkers in obese (n = 14; 30 ± 2 years; BMI 35 ± 1 kg•m−2) and non-obese (n = 16; 24 ± 2 years; BMI 23 ± 1 kg•m−2) women, in response to a high fat meal. Blood samples were collected pre-meal (fasted), and at 1, 2, 4 and 6 hours post meal, and assayed for trolox equivalent antioxidant capacity (TEAC), xanthine oxidase activity (XO), hydrogen peroxide (H2O2), malondialdehyde (MDA), triglycerides (TAG), and glucose. An obesity status effect was noted for all variables (p < 0.001; MDA p = 0.05), with obese women having higher values than non-obese, except for TEAC, for which values were lower. Time main effects were noted for all variables (p ≤ 0.01) except for TEAC and glucose, with XO, H2O2, MDA and TAG increasing following feeding with a peak response at the four or six hour post feeding time point. While values tended to decline by six hours post feeding in the non-obese women (agreeing with previous studies), they were maintained (MDA) or continued to increase (XO, H2O2 and TAG) in the obese women. While no interaction effects were noted (p > 0.05), contrasts revealed greater values in obese compared to non-obese women for XO, H2O2, MDA, TAG and glucose, and lower values for TEAC at times from 1–6 hours post feeding (p ≤ 0.03). We conclude that young, obese women experience a similar pattern of increase in blood oxidative stress biomarkers in response to a high fat meal, as compared to non-obese women. However, the overall oxidative stress is greater in obese women, and values appear to remain elevated for longer periods of time post feeding. These data provide insight into another potential mechanism related to obesity-mediated morbidity.
Oxidative Stress and Antioxidant Defense Mechanisms Linked to Exercise During Cardiopulmonary and Metabolic Disorders
Kelsey Fisher-Wellman,Heather K. Bell,Richard J. Bloomer
Oxidative Medicine and Cellular Longevity , 2009, DOI: 10.4161/oxim.2.1.7732
Abstract: Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS), evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary “signal” for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.
A Significant but Rather Mild Contribution of T286 Autophosphorylation to Ca2+/CaM-Stimulated CaMKII Activity
Steven J. Coultrap, Kelsey Barcomb, K. Ulrich Bayer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037176
Abstract: Background Autophosphorylation of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) at T286 generates partially Ca2+/CaM-independent “autonomous” activity, which is thought to be required for long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning and memory. A requirement for T286 autophosphorylation also for efficient Ca2+/CaM-stimulated CaMKII activity has been described, but remains controversial. Methodology/Principal Findings In order to determine the contribution of T286 autophosphorylation to Ca2+/CaM-stimulated CaMKII activity, the activity of CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared. As the absolute activity can vary between individual kinase preparations, the activity was measured in six different extracts for each kinase (expressed in HEK-293 cells). Consistent with measurements on purified kinase (from a baculovirus/Sf9 cell expression system), CaMKII T286A showed a mildly but significantly reduced rate of Ca2+/CaM-stimulated phosphorylation for two different peptide substrates (to ~75–84% of wild type). Additional slower CaMKII autophosphorylation at T305/306 inhibits stimulation by Ca2+/CaM, but occurs only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus, we tested if the T286A mutant may show more extensive inhibitory autophosphorylation, which could explain its reduced stimulated activity. By contrast, inhibitory autophosphorylation was instead found to be even further reduced for the T286A mutant under our assay conditions. On a side note, the phospho-T305 antibody showed some basal background immuno-reactivity also with non-phosphorylated CaMKII, as indicated by T305/306A mutants. Conclusions/Significance These results indicate that Ca2+/CaM-stimulated CaMKII activity is mildly (~1.2–1.3fold) further increased by additional T286 autophosphorylation, but that this autophosphorylation is not required for the major part of the stimulated activity. This indicates that the phenotype of CaMKII T286A mutant mice is indeed due to the lack of autonomous activity, as the T286A mutant showed no dramatic reduction in stimulated activity.
Postprandial Oxidative Stress in Exercise Trained and Sedentary Cigarette Smokers
Richard J. Bloomer,Kelsey H. Fisher-Wellman
International Journal of Environmental Research and Public Health , 2009, DOI: 10.3390/ijerph6020579
Abstract: Cigarette smokers experience an exaggerated triglyceride (TAG) and oxidative stress response to high fat feeding. Exercise training may serve to attenuate the rise in these variables, by improving TAG clearance and antioxidant defense. We compared blood TAG, antioxidant capacity, and oxidative stress biomarkers in exercise trained (>2 hrs per wk) and untrained smokers matched for age, in response to a high fat test meal. We report here that low volume exercise training can attenuate postprandial lipid peroxidation, but has little impact on blood TAG and other markers of oxidative stress. Higher volumes of exercise may be needed to allow for clinically meaningful adaptations in postprandial lipemia and oxidative stress.
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