196,900 research outputs found

    A Bisallylic Mini-lipoxygenase from Cyanobacterium Cyanothece sp That Has an Iron as Cofactor

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    Lipoxygenases are enzymes that are found ubiquitously in higher animals and plants, but have only recently been identified in a number of bacteria. The genome of the diazotrophic unicellular cyanobacterium Cyanothece sp. harbors two genes with homology to lipoxygenases. Here we describe the isolation of one gene, formerly named csplox2. It was cloned, and the protein was expressed in Escherichia coli and purified. The purified enzyme belongs to the group of prokaryotic mini lipoxygenases, because it had a molecular mass of 65 kDa. Interestingly, it catalyzed the conversion of linoleic acid, the only endogenously found polyunsaturated fatty acid, primarily to the bisallylic hydroperoxide 11R-hydroperoxyoctadecadienoic acid. This product had previously only been described for the manganese lipoxygenase from the take all fungus, Gaeumannomyces graminis. By contrast, CspLOX2 was shown to be an iron lipoxygenase. In addition, CspLOX2 formed a mixture of typical conjugated lipoxygenase products, e. g. 9R- and 13S-hydroperoxide. The conversion of linoleic acid took place with a maximum reaction rate of 31 s(-1). Incubation of the enzyme with [(11S)-(2)H] linoleic acid led to the formation of hydroperoxides that had lost the deuterium label, thus suggesting that CspLOX2 catalyzes antarafacial oxygenation as opposed to the mechanism of manganese lipoxygenase. CspLOX2 could also oxidize diarachidonylglycerophosphatidylcholine with similar specificity as the free fatty acid, indicating that binding of the substrate takes place with a "tail-first" orientation. We conclude that CspLOX2 is a novel iron mini-lipoxygenase that catalyzes the formation of bisallylic hydroperoxide as the major product

    Dr. Duane M. Jackson, Morehouse College, July 2011

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    This video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer

    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.

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    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states. By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement. To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports

    A PK-PD model for predicting the impact of age, CYP2C9, and VKORC1 genotype on individualization of warfarin therapy

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    The aim of this study was to characterize the relationship between warfarin concentrations and international normalized ratio (INR) response and to identify predictors important for dose individualization. S- and R-warfarin concentrations, INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/ pharmacodynamic model in NONMEM. The anticoagulant response was best described by an inhibitory EMAX model, with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. CYP2C9 genotype and age were identified as predictors for S-warfarin clearance, and VKORC1 genotype as a predictor for warfarin sensitivity. Predicted INR curves indicate important steady-state differences between patients with different sets of covariates; differences that cannot be foreseen from early INR assessments alone. It is important to account for CYP2C9 and VKORC1 genotypes and age to improve a priori and a posteriori individualization of warfarin therapy

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Dr. Glendon Swarthout

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    Hosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness

    Arabidopsis GH3 .10 conjugates jasmonates

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    Abstract Jasmonates regulate plant development and defence. In angiosperms, the canonical bioactive jasmonate is jasmonoyl‐isoleucine (JA‐Ile), which is formed in Arabidopsis thaliana by JAR1 and GH3.10. In contrast to other jasmonate biosynthesis or perception mutants, however, gh3.10 jar1 knockout lines are still fertile. Therefore we investigated whether further jasmonates and GH3 enzymes contribute to regulation of fertility. Jasmonate levels were analysed by liquid chromatography–mass spectrometry. The substrate range of recombinant GH3.10 and related GH3 enzymes was studied using non‐targeted ex vivo metabolomics with flower and leaf extracts of A. thaliana and in vitro enzyme assays. Jasmonate application experiments were performed to study their potential bioactivity. In flowers and wounded leaves of gh3.10 jar1 knockout lines JA‐Ile was below the detection limit. While 12‐hydroxy‐JA was identified as the preferred substrate of GH3.10, no other recombinant GH3 enzymes tested were capable of JA‐Ile formation. Additional JA conjugates found in wounded leaves (JA‐Gln) or formed in flowers upon MeJA treatment in the absence of JA‐Ile (JA‐Gln, JA‐Asn, JA‐Glu) were identified. The aos gh3.10 jar1 was introduced as a novel tool to test for the bioactivity of JA‐Gln to regulate fertility. This study found JAR1 and GH3.10 are the only contributors to JA‐Ile biosynthesis in Arabidopsis and identified a number of JA conjugates as potential bioactive jasmonates acting in the absence of JA‐Ile. However, their contribution in regulating fertility is yet to be conclusively determined.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165

    A pharmacometric model describing the relationship between warfarin dose and INR response with respect to variations in CYP2C9, VKORC1, and age

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    The objective of the study was to update a previous NONMEM model to describe the relationship between warfarin dose and international normalized ratio (INR) response, to decrease the dependence of the model on pharmacokinetic (PK) data, and to improve the characterization of rare genotype combinations. The effects of age and CYP2C9 genotype on S-warfarin clearance were estimated from high-quality PK data. Thereafter, a temporal dose-response (K-PD) model was developed from information on dose, INR, age, and CYP2C9 and VKORC1 genotype, with drug clearance as a covariate. Two transit compartment chains accounted for the delay between exposure and response. CYP2C9 genotype was identified as the single most important predictor of required dose, causing a difference of up to 4.2-fold in the maintenance dose. VKORC1 accounted for a difference of up to 2.1-fold in dose, and age reduced the dose requirement by similar to 6% per decade. This reformulated K-PD model decreases dependence on PK data and enables robust assessment of INR response and dose predictions, even in individuals with rare genotype combinations
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