939 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

    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

    Peer culture in preschool : A study of preschool teachers' attitudeand way of working

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    Arbetets art: Examensarbete i lärarutbildningen, avancerad nivå, 15hp. Högskolan   Skövde.   Titel: Kamratkultur i förskolan. En studie om förskollärares förhållningssätt och arbetssätt.   Sidantal: 32   Författare: Ida Christesen, Helen Fredriksson och Malin Hamberg   Handledare: Mirella Forsberg Ahlcrona   Datum: 7 januari 2013   Nyckelord: Förskola, kamratkultur, gemenskap, samhörighet, uteslutning och etik   Denna studie belyser kamratkulturer i förskolan mot bakgrund av förskollärares förhållningssätt och arbetssätt. Med kamratkultur, menar vi gemenskap, samhörighet och uteslutning. Studiens teoretiska perspektiv tar sin utgångspunkt i det sociokulturella perspektivet. Vi har i denna studie genomfört tolv kvalitativa intervjuer.  Resultatet visar att förskollärare använder sig av snarlika metoder för att stödja barnen i deras gemenskap och samhörighet. Det visar sig också att förskollärare har olika strategier för att hjälpa barn komma in i leken, bland annat genom att göra barn ”attraktiva” för varandra, som ett sätt att motverka uteslutning bland barn i förskolan.Study: Degree project in teacher education, advanced level, 15 hp. University of Skövde   Title: Peer culture in preschool. A study of preschool teachers’ attitude and way of working   Number of pages: 32   Author: Ida Christesen, Helen Fredriksson and Malin Hamberg   Tutor: Mirella Forsberg Ahlcrona   Date: 7th of January 2013   Keywords: Preschool, peer culture, fellowship, togetherness, exclusion and ethics   This study highlights the peer cultures of preschool on the basis of preschool teachers' attitudes and practices. With peer culture, we mean fellowship, togheterness and exclusion. The theoretical approach is based on the socio-cultural perspective. We have in this study carried through twelve qualitative interviews. The result shows that preschool teachers use similar methods to support children in their fellowship and togetherness. It also turns out that preschool teachers have different strategies to help children enter the play activity, for instance making children "attractive" for each other, as a way to work against exclusion among children in preschool

    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

    Distinguishing models of new physics at the LHC

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    The work presented in this thesis explores ways of distinguishing models of physics beyond the Standard Model at the Large Hadron Collider (LHC). The focus is puton supersymmetric models, in particular the Minimal Supersymmetric Standard Model (MSSM) and the E6-inspired Supersymmetric Standard Model (E6SSM), which are wellknown and well motivated models.The muon decay channel of the pseudoscalar and heavy Higgs bosons in the MSSM is studied. It is shown that these decays to muons, in some scenarios, make it possible to measure the widths of these Higgs bosons at the LHC. This is the only known way of measuring this width at the LHC. The decays to muons also allow for the mass to be measured accurately which together with the width measurement offers a uniqueopportunity to pin down the value of the model parameter tan Beta, which could be used to distinguish different scenarios within the MSSM and potentially in its extensions.Gluino cascade decays are investigated as a tool to distinguish the MSSM from more complex models, with the E6SSM as an example. It is shown that the longer cascadedecays of the E6SSM gluinos provide less missing transverse momentum and higher lepton multiplicity, implying the higher importance of multi-lepton searches at the LHC in models with a richer low-energy particle content. The three-lepton channel is shown to be a good discriminator between the models. In the case of a gluino discovery one would typically expect a signal in this channel if it is an E6SSM gluino but not if it is an MSSM gluino.Furthermore, the implications of limits from dark matter and Z' searches on the Higgs sector and other collider phenomenology are discussed. These implications are important to constrain and differentiate models. In addition, the contribution to fine-tuning from the Z' mass is discussed as an important measure of how attractive a model is, which should be considered by model builder

    Differential susceptibility of Iowa waterhemp (Amaranthus tuberculatus) populations to 2,4-D, dicamba, and glufosinate

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    Multiple herbicide-resistant waterhemp (Amaranthus tuberculatus (Moq.) J.D. Sauer) has limited herbicide options for Iowa row crop production. Soybean (Glycine max (L.) Merr.) cultivars and corn (Zea mays L.) hybrids resistant to 2,4-D, dicamba, and glufosinate have provided more herbicide options for waterhemp management. A probability-based survey of Iowa fields was conducted in fall 2019 wherein waterhemp seeds were collected and their susceptibility to 2,4-D, dicamba, and glufosinate was determined. The average survival of all populations treated with 1× 2,4-D, dicamba, and glufosinate was 17%, 5%, and 4%, respectively. Seven percent of treated populations exhibited ≥50% survival to 1× rates of 2,4-D.This article is published as Ryan C. Hamberg, Ramawatar Yadav, Micheal D.K. Owen, and Mark A. Licht. Differential susceptibility of Iowa waterhemp (Amaranthus tuberculatus) populations to 2,4-D, dicamba, and glufosinate. Canadian Journal of Plant Science. (2023). https://doi.org/10.1139/cjps-2023-0081. © 2023 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited
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