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  • 301.
    Emanuelsson, Rikard
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Wallner, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ng, Eugene A. M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Smith, J. R.
    Nauroozi, Djawed
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Ott, Sascha
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Cross-hyperconjugation: An unexplored orbital interaction between pi-conjugated and saturated molecular segments2013Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, nr 3, s. 983-987Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Crossing a barrier: Molecules with saturated ER2 units (E=C or Si, R=electron-releasing group) inserted between two π-conjugated segments have electronic and optical properties that resemble those of cross-conjugated molecules (see figure). This cross-hyperconjugation provides a deeper understanding of the conjugation phenomenon, and is an alternative to cross-conjugation in the design of molecules for nano and materials applications.

  • 302. Endale, Milkyas
    et al.
    Alao, John Patrick
    Akala, Hoseah M
    Rono, Nelson K
    Eyase, Fredrick L
    Derese, Solomon
    Ndakala, Albert
    Mbugua, Martin
    Walsh, Douglas S
    Sunnerhagen, Per
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Yenesew, Abiy
    Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata.2012Inngår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 78, nr 1, s. 31-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

  • 303. Endale, Milkyas
    et al.
    Ekberg, Annabel
    Akala, Hoseah M
    Alao, John Patrick
    Sunnerhagen, Per
    Yenesew, Abiy
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Busseihydroquinones A-D from the roots of Pentas bussei2012Inngår i: Journal of Natural Products, ISSN 0163-3864, E-ISSN 1520-6025, Vol. 75, nr 7, s. 1299-1304Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Four new naphthohydroquinones, named busseihydroquinones A-D (1-4), along with a known homoprenylated dihydronaphthoquinone (5), were isolated from the CH(2)Cl(2)/MeOH (1:1) extract of the roots of Pentas bussei. Although the genus Pentas is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquine-resistant (W2) strains of Plasmodium falciparum were observed for the crude root extract and the isolated constituents of this plant.

  • 304. Engberg, A. E.
    et al.
    Nilsson, P. H.
    Sandholm, K.
    Huang, S.
    Mollnes, T. E.
    Nicholls, I. A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Nilsson, B.
    Ekdahl, K. N.
    The ratio between C4 and C4BP adsorbed to artificial materials is a new predictor for biocompatibility2013Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 56, nr 3 SI, s. 309-309Artikkel i tidsskrift (Annet vitenskapelig)
  • 305. Engberg, Anna E.
    et al.
    Nilsson, Per H.
    Huang, Shan
    Fromell, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hamad, Osama A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Mollnes, Tom Eirik
    Rosengren-Holmberg, Jenny P.
    Sandholm, Kerstin
    Teramura, Yuji
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Ekdahl, Kristina N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, s. 55-65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.

  • 306.
    Engler, Henry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Nennesmo, Inger
    Kumlien, Eva
    Gambini, JP
    Lundberg, PO
    Savitcheva, Irina
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Imaging astrocytosis with PET in Creutzfeldt-Jakob disease: case report with histopathological findings2012Inngår i: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, nr 2, s. 201-207Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In a previous study, patients with suspect Creutzfeldt-Jakob's disease (CJD) have been examined with Positron Emission Tomography (PET) combining N-[11C-methyl]-L-deuterodeprenyl (DED) and [(18)F] 2- fluorodeoxyglucose (FDG) in an attempt to detect astrocytosis and neuronal dysfunction, two of the hallmarks in CJD. Increased DED uptake with pronounced hypometabolism matching the areas with high DED retention was found in the fronto-parieto-occipital areas and cerebellum of patients with confirmed CJD. However, the temporal lobes did not present such a pattern. In 6 of the 15 examined patients the autopsy was performed, but a strict comparison between the PET results and the histopathology could not be done. Recently, one patient with suspect CJD was examined with PET using DED and FDG. The results of the examinations in this patient showed a pattern similar to that found in the brain of the CJD patients from the first study. The patient died shortly after the examination and an autopsy could be performed. The autopsy showed neuronal death, astrocytosis and spongiform changes in the brain. The diagnosis of definite sporadic CJD was established by the Western blot analysis, confirming the presence of the prion resistant protein (PrPres). The PET data demonstrated high DED uptake and extreme low glucose uptake in the left brain hemisphere whereas the right side was less affected. The autopsy was performed allowing the comparison between high DED uptake and the histopathological findings of reactive astrocytosis revealed by immunostaining with antibodies against glial fibrillary acid protein (GFAP). The results confirmed the presence of a pattern with high ratio DED/FDG, similar to that found in the previous study and revealing for the first time, a good correlation between high DED uptake and high density of reactive astrocytes as demonstrated by immunostaining.

  • 307.
    Englund, Elias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Pattanaik, Bagmi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Ubhayasekera, Sarojini J.K.A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Stensjö, Karin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Lindberg, Pia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Production of Squalene in Synechocystis sp. PCC 68032014Inngår i: PLoS ONE, Vol. 9, nr 3, s. e90270-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In recent years, there has been an increased interest in the research and development of sustainable alternatives to fossil fuels. Using photosynthetic microorganisms to produce such alternatives is advantageous, since they can achieve direct conversion of carbon dioxide from the atmosphere into the desired product, using sunlight as the energy source. Squalene is a naturally occurring 30-carbon isoprenoid, which has commercial use in cosmetics and in vaccines. If it could be produced sustainably on a large scale, it could also be used instead of petroleum as a raw material for fuels and as feedstock for the chemical industry. The unicellular cyanobacterium Synechocystis PCC 6803 possesses a gene, slr2089, predicted to encode squalene hopene cyclase (Shc), an enzyme converting squalene into hopene, the substrate for forming hopanoids. Through inactivation of slr2089 (shc), we explored the possibility to produce squalene using cyanobacteria. The inactivation led to accumulation of squalene, to a level over 70 times higher than in wild type cells, reaching 0.67 mg OD750−1 L−1. We did not observe any significant growth deficiency in the Δshc strain compared to the wild type Synechocystis, even at high light conditions, suggesting that the observed squalene accumulation was not detrimental to growth, and that formation of hopene by Shc is not crucial for growth under normal conditions, nor for high-light stress tolerance. Effects of different light intensities and growth stages on squalene accumulation in the Δshc strain were investigated. We also identified a gene, sll0513, as a putative squalene synthase in Synechocystis, and verified its function by inactivation. In this work, we show that it is possible to use the cyanobacterium Synechocystis to generate squalene, a hydrocarbon of commercial interest and a potential biofuel. We also report the first identification of a squalene hopene cyclase, and the second identification of squalene synthase, in cyanobacteria.

  • 308.
    Engman, Jonas
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Åhs, Fredrik
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Furmark, Tomas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Linnman, Clas
    Pissiota, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Appel, Lieuwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Frans, Örjan
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Fredrikson, Mats
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Age, sex and NK1 receptors in the human brain: A positron emission tomography study with [C-11]GR2051712012Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, nr 8, s. 562-568Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n = 9) and women (n = 9) matched for age varying between 20 and 50 years using the highly specific NK1 receptor antagonist [11C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence.

  • 309.
    Engman, Mattias
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Cheruku, Pradeep
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Kaukoranta, Päivi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Völker, Sebastian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Andersson, Pher
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Highly Selective Iridium-Catalyzed Asymmetric Hydrogenation of Trifluoromethyl Olefins: A New Route to Trifluoromethyl- Bearing Stereocenters2009Inngår i: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 351, nr 3, s. 375-378Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fluorine-containing compounds are useful in many applications ranging from pharmaceuticals to ferroelectric crystals. We have developed a new, highly enantioselective synthetic route to trifluoromethyl-bearing stereocenters in up to 96% ee via asymmetric hydrogenation using N,P-ligated iridium catalysts. We also hydrogenated an isomeric mixture of olefins; this reaction gave the hydrogenation product highly enantioselectively (87% ee), and only the E isomer was present after the reaction had reached 56% conversion.

  • 310.
    Engström, Lorentz
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Zetterqvist, Örjan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ragnarsson, Ulf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Ek, Pia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Dahlqvist-Edberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The cyclic AMP-dependent phosphorylation of pyruvate kinase as a model in the study of regulation and turnover of phosphorylated proteins1982Inngår i: Progress in clinical and biological research, ISSN 0361-7742, Vol. 102, nr Pt C, s. 203-212Artikkel i tidsskrift (Fagfellevurdert)
  • 311.
    Enugala, Thilak Reddy
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Engineered Alcohol Dehydrogenases for Stereoselective Chemical Transformations2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Enzymes are biomolecules built from amino acids and catalyze the chemical transformations in a cell. Enzymes are by nature stereoselective, biodegradable, environmentally friendly, and can perform catalysis in aqueous solutions and at ambient temperatures. Due to these advantages the use of enzymes as biocatalysts for chemical transformations has emerged as an attractive “greener” alternative to conventional chemical synthesis strategies. And, if naturally occurring enzymes cannot carry out the desired chemical transformations, the functional properties of enzymes can be modified by directed evolution or protein engineering techniques. Since enzymes are genetically encoded they can be optimized for desired traits such as substrate selectivity or improved catalytic efficiency. Considering these advantages and also keeping the synthetic and industrial application in mind, we have employed alcohol dehydrogenase-A (ADH-A) from Rhodococcus ruber DSM 44541 as a study object in engineering for new catalytic properties. ADH-A tolerates water miscible organic solvents, accepts a relatively wide range of aromatic sec-alcohols/ketones as substrates and is therefore a potentially useful biocatalyst for asymmetric synthesis of organic compounds.

     

    Presented research work in this thesis has been primarily focused on engineering of ADH-A and characterization of resulting enzyme variants. The engineering efforts have aimed for altered substrate scope, as well as stereo- and regioselectivities. Furthermore, possible substrate promiscuity in engineered enzyme variants has also been addressed. In short, i). Paper I: three sub sites, each consisting of two-three amino acid residues within the active-site cavity were exposed to saturation mutagenesis in step-wise manner, coupled to an in vitro selection for improved catalytic activity with the unfavored (R)-1-phenylethanol. The observed stereoselectivity could be explained partly by a shift in nonproductive substrate binding. ii). Paper II is aimed specifically towards the improving the catalytic activity with aryl-substituted vicinal diols, such as (R)-1-phenylethane-1,2-diol, and the possibility to link the ADH-A reaction with a preceding epoxide hydrolysis to produce the acyloin 2-hydroxyacetophenone from rac-styrene oxide. iii). Paper III is mainly focused towards studies of regioselectivity. Here, ADH-A and engineered variants were challenged with a substrate containing two sec-alcohol functions and the cognate di-ketone. The regioselectivity in wild type as well as in engineered variants could in part be explained by a combination of experimental and computer simulations. iv). Paper IV is focused on elucidating possible effects on substrate promiscuities in engineered variants as compared to the wild type parent enzyme, when challenged with a spectrum of potential previously untested substrates.

    Delarbeid
    1. Relaxation of Nonproductive Binding and Increased Rate of Coenzyme Release in an Alcohol Dehydrogenase Increases Turnover With a Non-Preferred Alcohol Enantiomer
    Åpne denne publikasjonen i ny fane eller vindu >>Relaxation of Nonproductive Binding and Increased Rate of Coenzyme Release in an Alcohol Dehydrogenase Increases Turnover With a Non-Preferred Alcohol Enantiomer
    Vise andre…
    2017 (engelsk)Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 284, nr 22, s. 3895-3914Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Alcohol dehydrogenase A (ADH-A) from Rhodococcus ruber DSM 44541 is a promising biocatalyst for redox transformations of arylsubstituted sec-alcohols and ketones. The enzyme is stereoselective in the oxidation of 1-phenylethanol with a 300-fold preference for the (S)-enantiomer. The low catalytic efficiency with (R)-1-phenylethanol has been attributed to nonproductive binding of this substrate at the active site. Aiming to modify the enantioselectivity, to rather favor the (R)-alcohol, and also test the possible involvement of nonproductive substrate binding as a mechanism in substrate discrimination, we performed directed laboratory evolution of ADH-A. Three targeted sites that contribute to the active-site cavity were exposed to saturation mutagenesis in a stepwise manner and the generated variants were selected for improved catalytic activity with (R)-1-phenylethanol. After three subsequent rounds of mutagenesis, selection and structure-function analysis of isolated ADH-A variants, we conclude: (1) W295 has a key role as a structural determinant in the discrimination between (R)- and (S)-1-phenylethanol and a W295A substitution fundamentally changes the stereoselectivity of the protein. One observable effect is a faster rate of NADH release, which changes the rate-limiting step of the catalytic cycle from coenzyme release to hydride transfer. (2) The obtained change in enantiopreference, from the (S)- to the (R)-alcohol, can be partly explained by a shift in the nonproductive substrate binding modes.

    Emneord
    alcohol dehydrogenase, biocatalysis, stereoselectivity, directed evolution, crystal structures, enzyme kinetics
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-318981 (URN)10.1111/febs.14279 (DOI)000415877100011 ()
    Forskningsfinansiär
    Swedish Research Council, 621-2011-6055
    Tilgjengelig fra: 2017-03-30 Laget: 2017-03-30 Sist oppdatert: 2019-10-21bibliografisk kontrollert
    2. Directed Evolution of Alcohol Dehydrogenase for Improved Stereoselective Redox Transformations of 1-Phenylethane-1,2-Diol and Its Corresponding Acyloin
    Åpne denne publikasjonen i ny fane eller vindu >>Directed Evolution of Alcohol Dehydrogenase for Improved Stereoselective Redox Transformations of 1-Phenylethane-1,2-Diol and Its Corresponding Acyloin
    Vise andre…
    2018 (engelsk)Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 57, s. 1059-1062Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Laboratory evolution of alcohol dehydrogenase produced enzyme variants with improved turnover numbers with a vicinal 1,2-diol and its corresponding hydroxyketone. Crystal structure and transient kinetics analysis aids in rationalizing the new functions of these variants.

    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-340574 (URN)10.1021/acs.biochem.8b00055 (DOI)000426013300003 ()29384657 (PubMedID)
    Forskningsfinansiär
    Stiftelsen Olle Engkvist Byggmästare, 183-358
    Tilgjengelig fra: 2018-01-31 Laget: 2018-01-31 Sist oppdatert: 2019-10-21bibliografisk kontrollert
    3. Stereo- and Regioselectivity in Catalyzed Transformation of a 1,2-Disubstituted Vicinal Diol and the Corresponding Diketone by Wild Type and Laboratory Evolved Alcohol Dehydrogenases
    Åpne denne publikasjonen i ny fane eller vindu >>Stereo- and Regioselectivity in Catalyzed Transformation of a 1,2-Disubstituted Vicinal Diol and the Corresponding Diketone by Wild Type and Laboratory Evolved Alcohol Dehydrogenases
    Vise andre…
    2018 (engelsk)Inngår i: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, nr 8, s. 7526-7538Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ADH-A from Rhodococcus ruber DSM 44541 catalyzes the oxidation of (S)-1-phenylethanol 3000-fold more efficiently as compared with the 2-hydroxylated derivative (R)-phenylethane-1,2-diol. The enzyme is also highly selective for sec-alcohols with comparably low activities with the corresponding primary alcohols. When challenged with a substrate containing two secondary alcohols, such as 1-phenylpropane-(1R,2S)-diol, ADH-A favors the oxidation of the benzylic carbon of this alcohol. The catalytic efficiency, however, is modest in comparison to the activity with (S)-1-phenylethanol. To investigate the structural requirements for improved oxidation of vicinal diols, we conducted iterative saturation mutagenesis combined with activity screening. A first-generation variant, B1 (Y54G, L119Y) displays a 2-fold higher kcat value with 1-phenylpropane-(1R,2S)-diol and a shift in the cooperative behavior in alcohol binding, from negative in the wild type, to positive in B1, suggesting a shift from a less active enzyme form (T) in the wild type to a more active form (R) in the B1 variant. Also, the regiopreference changed to favor oxidation of C-2. A second-generation variant, B1F4 (F43T, Y54G, L119Y, F282W), shows further improvement in the turnover and regioselectivity in oxidation of 1-phenylpropane-(1R,2S)-diol. The crystal structures of the B1 and B1F4 variants describe the structural alterations to the active site, the most significant of which is a repositioning of a Tyr side-chain located distal to the coenzyme and the catalytic zinc ion. The links between the changes in structures and stereoselectivities are rationalized by molecular dynamics simulations of substrate binding at the respective active sites.

    Keywords: alcohol dehydrogenase; alcohol oxidation; biocatalysis; crystal structure; directed evolution; enzyme engineering; molecular dynamics simulations; stereoselectivity

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-355854 (URN)10.1021/acscatal.8b01762 (DOI)000441112400074 ()
    Forskningsfinansiär
    Stiftelsen Olle Engkvist ByggmästareSwedish Research Council, 2015-04928Knut and Alice Wallenberg Foundation, KAW 2013.0124EU, FP7, Seventh Framework Programme, 283570Swedish National Infrastructure for Computing (SNIC), 2015/16-12Swedish National Infrastructure for Computing (SNIC), 2016/34-27
    Tilgjengelig fra: 2018-07-05 Laget: 2018-07-05 Sist oppdatert: 2019-10-21bibliografisk kontrollert
    4. Substrate Promiscuity in In-Vitro Evolved Alcohol Dehydrogenases
    Åpne denne publikasjonen i ny fane eller vindu >>Substrate Promiscuity in In-Vitro Evolved Alcohol Dehydrogenases
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Forskningsprogram
    Biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-395439 (URN)
    Tilgjengelig fra: 2019-10-18 Laget: 2019-10-18 Sist oppdatert: 2019-10-21
  • 312.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    15N NMR chemical shift in the characterisation of halogen bonding in solution2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    15N NMR chemical shift in the characterisation of halogen bonding in solution  

    Sebastiaan B. Hakkert, Jürgen Gräfenstein and Mate Erdelyi*   

    NMR chemical shift changes induced upon formation of non-covalent interactions have been used as sensitive and specific observables in the evaluation of weak chemical forces in solutions, among others of halogen bonding.1 1H NMR has high sensitivity yet a narrow chemical shift range, ca 10 ppm, resulting in small and thus difficult to measure chemical shift changes upon binding. In contrast, 13C NMR offers a wider shift range, ca 200 ppm, providing larger chemical shift changes upon weak binding to be detected; however, its low sensitivity limits its applicability. 19F NMR provides high sensitivity and a wide chemical shift range, ca 500 ppm, and hence is straightforwardly applicable on substances that possess a fluorine close to the halogen bond donor site,2 but is unfortunately often unavailable for real-life substances applied in medicinal chemistry, for example, typically missing fluorine substitution. 15N NMR despite its low sensitivity, which can be overcome by indirect detection experiments (HMBC), provides several advantages, such as an unusually wide chemical shift range, ca 900 ppm, and most importantly the detectability of halogen and hydrogen bonds directly at the Lewis base involved in the interaction. Accordingly, upon formation of a halogen bond with a nitrogen donor ligand typically 10-20 ppm,3 and for very strong interactions up to 100 ppm,4 15N chemical shift changes have been reported.  

    In this project we have evaluated the capability of 15N NMR to describe halogen bonding interactions with respect to solvent and electronic effects, and the alteration of N-X bond lengths. The observations made for halogen bonds were compared to those obtained for analogous hydrogen bonding systems using the same nitrogen donor halogen/hydrogen bond acceptor. The experimental data obtained on an 800 MHz spectrometer was compared to and interpreted with the help of computational data (DFT).The observed chemical shift changes upon formation of halogen bonds were correlated to various descriptors to understand their origin. Based on the above data the scope and limitations of 15N NMR for detection and understanding of halogen bonding in solution will be discussed.

    References

    1. Bertrán, J. F.; Rodríguez, M. Org. Magn. Reson. 1979, 12, 92, 1980, 14, 244; 1981, 16, 79.

    2. Metrangolo, P.; Panzeri, W.; Recupero F; Resnati, G. J. Fluorine Chem. 2002, 114, 27.

    3. Castro-Fernandez, S.; Lahoz, I. R.; Llamas-Saiz, A. L.; Alonso-Gomez, J. L.; Cid, M. M.; Navarro-Vazquez, A. Org. Lett. 2014, 16, 1136; Puttreddy, R.; Jurcek, O.; Bhowmik, S.; Makela, T.; Rissanen, K. Chem. Commun. 2016, 52, 2338.

    4. Carlsson, A.-C. C.; Grafenstein, J.; Budnjo, A.; Laurila, J. L.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706

  • 313.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halogen and hydrogen bonding -: computationally supported NMR spectroscopy2017Konferansepaper (Fagfellevurdert)
  • 314.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Halogen Bonding:: An Alternative Tool to Modulate Peptide Conformation2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halogen bonding: an alternative tool to modulate peptide conformation

    Emma Danelius(1), Hanna Andersson(1), Patrik Jarvoll(1), Kajsa Lood(1), Jürgen Gräfenstein(1) and  Mate Erdelyi(1,2)

    1) Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden

    2) Department of Chemistry – BMC, Uppsala University, Sweden   

    Halogen bonding is a weak chemical force that resembles hydrogen bonding in many aspects. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has so far rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. 

    The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. 

    A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a β-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.  

  • 315.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    ParLig:: Paramagnetic Ligand Tagging to Identify Protein Binding Sites2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    ParLig: Paramagnetic Ligand Tagging to  Identify Protein Binding Sites

    Ulrika Brath,1 Shashikala I. Swamy,1 Alberte X. Veiga,1 Ching-Chieh Tung,2 Filip Van Petegem,2 Mate Erdelyi1*

    Department of Chemistry & Molecular Biology and the Swedish NMR Centre, University of Gothenburg,Sweden

    Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, Canada  

    Abstract: Identification of the binding site and binding mode of low affinity ligands, such as screening hits, is essential for the development of pharmaceutical leads using rational drug design strategies. We introduce ParLig, a paramagnetic ligand tagging approach that enables localization of protein – ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. Its scope is demonstrated by identification of the low mM volatile anesthetic interaction site of calmodulin. The technique provides an efficient route to rapid screening of protein – ligand systems, and to the identification of the binding site and mode of low affinity complexes.

    References: 

    1. Brath, U., Swami, S.I., Veiga, A.X., Tung, C.-C., Van Petegem, F., Erdelyi, M., J. Am. Chem Soc. 137, 11391-11398 (2015) .

  • 316.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pentacoordinate carbonium ions in solution2018Konferansepaper (Fagfellevurdert)
  • 317.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Solid-phase methods for the synthesis of heterocycles2006Inngår i: Microwave-Assisted  Synthesis of Heterocycles, Topics in Heterocyclic Chemistry, Berlin/Heidelberg, Germany: Springer GmbH & Co KB, Berlin/Heidelberg, Germany , 2006, s. 79-128Kapittel i bok, del av antologi (Fagfellevurdert)
  • 318.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The three-center halogen bond2019Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halonium ions, X+, play important roles in chemistry. In halogenation reactions, they are transferred from a halogen donor, D, to an acceptor, A, in the formally stepwise process D+- X + A →[D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A]+→ [D∙∙∙X-A]  → D + X-A+. The same process takes place when a halogen moves from a halogen bond [1] acceptor to another one within a complex, that has so far mostly been studied in model systems with the two donor sites possessing comparable Lewis basicities (A ~ D) [2-5]. Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases, with the bonds having varying degrees of covalency and secondary character [2].  Halonium ions are strong halogen bond donors that prefer to form a three-center geometry, [D∙∙∙X∙∙∙D]+, in which both D-X halogen bonds have partial covalent and partial secondary characters [2-6].

    In this talk, the influence of electronic and steric factors, solvent polarity and counterions, and of the type of the halogen on the geometry and reactivity of [D∙∙∙X∙∙∙D]+ halogen bond complexes will be discussed. The symmetric state, [D∙∙∙X∙∙∙D]+, is demonstrated to be strongly preferred over the alternative asymmetric arrangements [D∙∙∙X-D]+. Understanding the three-center halogen bonds provides insights into the fundamentals of the halogen bonding phenomenon and of halonium transfer reactions. The studied complexes are isoelectronic to the transition state of SN2 reactions, and thus may provide model systems for the exploration of fundamental reaction mechanisms.

    The synthesis, and the NMR spectroscopic and computational (DFT) studies of a variety of three-center halogen bond systems [2-6] will be presented focusing on the influence of steric and electronic factors on the geometry and electronic character of the three-center-fourelectron halogen bond.

    References 1. Halogen bonding is the noncovalent interaction of halogen in which they act as electron acceptors. 2. Karim, A.; Reitti, M.; Carlsson, A.-C.C.; Gräfenstein, J.; Erdelyi, M. Chem. Sci. 2014, 5, 3226. 3. Carlsson, A.-C.C.; Mehmeti, K.; Uhrbom, M.; Karim, A.; Bedin, M.; Puttreddy, R.; Kleinmaier, R.; Neverov, A.; Nekoueishahraki, B.; Gräfenstein, J.; Rissanen, K.; Erdelyi, M., J. Am. Chem. Soc. 2016, 138, 9853. 4. Carlsson, A.-C.C.; Gräfenstein,J.; Budnjo, A.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706.  5. Hakkert, S.B.; Erdelyi, M. J. Phys. Org. Chem. 2015, 28, 226. 6.Lindblad, S.; Mehmeti, K.; Veiga, A.; Nekoueishahraki, B.; Gräfenstein, J.; Erdelyi, M. J. Am. Chem. Soc.2018, 140, 13503.

  • 319.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    The three-centered halogen bond2018Konferansepaper (Fagfellevurdert)
  • 320.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    d’Auvergne, E.
    Navarro-Vazquez, A.
    Griesinger, C.
    Dynamics of the glycosidic linkage: conformational space of lactose2011Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 17, nr 34, s. 9368-9376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dynamics of the glycosidic bond of lactose was studied by a paramagnetic tagging‐based NMR technique, which allowed the collection of an unusually large series of NMR data for a single compound. By the use of distance‐ and orientation‐dependent residual dipolar couplings and pseudocontact shifts, the simultaneous fitting of the probabilities of computed conformations and the orientation of the magnetic susceptibility tensor of a series of lanthanide complexes of lactose show that its glycosidic bond samples syn/syn, anti/syn and syn/anti ϕ/ψ regions of the conformational space in water. The analysis indicates a higher reliability of pseudocontact shift data as compared to residual dipolar couplings with the presently available weakly orienting paramagnetic tagging technique. The method presented herein allows for an improved understanding of the dynamic behaviour of oligosaccharides.

  • 321.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Adolf
    Rapid Microwave-assisted solid-phase peptide synthesis2003Konferansepaper (Fagfellevurdert)
  • 322.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Gogoll, Aldof
    Development of a stilbene-type photoswitchable β-hairpin mimetic2005Konferansepaper (Fagfellevurdert)
  • 323.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Karlén, A.
    Gogoll, Aldolf
    Studies of Photoswitchable β-Hairpin Mimetics2003Konferansepaper (Fagfellevurdert)
  • 324.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Langer, V.
    Karlén, A.
    Gogoll, Adolf
    Structural Studies of Diastereomeric β-Hairpin Mimetics2002Konferansepaper (Fagfellevurdert)
  • 325.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Lindblad, Sofia
    Mehmeti, Krenare
    Veiga, Alberte X
    Nekoueishahraki, Bijan
    Gräfenstein, Jurgen
    The Halogen Bond of Halonium Ions2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Halonium ions, X+ , play important roles in chemistry. In halogenation reactions, they are transferred from a donor, D, to an acceptor, A, in the formally stepwise process D-X + A

    → [D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A][D∙∙∙X - A]+ → D + X - A+. The same process takes place when a halogen moves from a halogen bond donor to an acceptor within a complex, which has been studied so far mostly in model systems in which the donor and the acceptor possess comparable Lewis basicities (A ~ D) [1-4].  Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases that may possess varying degrees of covalency and secondary character [1]. Halonium ions are strong halogen bond donors that prefer to form a symmetric geometry, [D∙∙∙X∙∙∙D]+, with two D-X bonds of partial covalent and partial secondary character. This symmetric state is much preferred over the asymmetric alternative arrangement, [D∙∙∙X - D]+[1-4].

    We have explored how electronic and steric factors influence the electron density distribution and the geometry of [D∙∙∙X∙∙∙D]+-type complexes. Understanding this provides insights into the fundamental details of halonium transfer reactions, halogen transfer processes within halogen bonded systems as well as into important reaction mechanisms, such as SN2.

    In this talk the synthesis, NMR spectroscopic and computational (DFT) studies of so far undiscussed systems [5] will be presented, and the influence of steric and electronic factors on the geometry and electronic character of the three-center-four-electron halogen bond will be discussed.

  • 326.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Navarro-Vázquez, Armando
    Pfeiffer, Bernhard
    Kuzniewski, Christian N
    Felser, Andrea
    Widmer, Toni
    Gertsch, Jürg
    Pera, Benet
    Díaz, José Fernando
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    The binding mode of side chain- and C3-modified epothilones to tubulin2010Inngår i: ChemMedChem, ISSN 1860-7179, E-ISSN 1860-7187, Vol. 5, nr 6, s. 911-920Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of beta-His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.

  • 327.
    Erdélyi, Máté
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pfeiffer, Bernhard
    Hauenstein, Kurt
    Fohrer, Jörg
    Gertsch, Jürg
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    Conformational preferences of natural and C3-modified epothilones in aqueous solution.2008Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 51, nr 5, s. 1469-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

  • 328.
    Ericsson, Maria
    et al.
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Fallahsharoudi, Amir
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. ARUP Institute for Clinical & Experimental Pathology, Salt Lake City, UT, USA AND Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
    Kushnir, Mark M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. ARUP Institute for Clinical & Experimental Pathology, Salt Lake City, UT, USA AND Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
    Jensen, Per
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Domestication effects on behavioural and hormonal responses to acute stress in chickens2014Inngår i: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 133, s. 161-169Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Comparative studies have shown that alterations in physiology, morphology and behaviour have arisen due to the domestication. A driving factor behind many of the changes could be a shift in stress responses, with modified endocrine and behavioural profiles. In the present study we compared two breeds of chicken (Gallus gallus), the domestic White Leghorn (WL) egg laying breed and its ancestor, the Red Junglefowl (RJF). Birds were exposed to an acute stress event, invoked by 3 or 10 min of physical restraint. They were then continuously monitored for the effects on a wide range of behaviours during a 60 min recovery phase. Blood samples were collected from the chicken at baseline, and after 10 and 60 min following a similar restraint stress, and the samples were analyzed for nine endogenous steroids of the HPA and HPG axes. Concentration of the steroids was determined using validated liquid chromatography tandem mass spectrometry methods. In RJF, an immediate behavioural response was observed after release from restraint in several behaviours, with a relatively fast return to baseline within 1 h. In WL, some behaviours were affected for a longer period of time, and others not at all. Concentrations of corticosterone increased more in RJF, but returned faster to baseline compared to WL. A range of baseline levels for HPG-related steroids differed between the breeds, and they were generally more affected by the stress in WL than in RJF. In conclusion, RJF reacted stronger both behaviourally and physiologically to the restraint stress, but also recovered faster. This would appear to be adaptive under natural conditions, whereas the stress recovery of domesticated birds has been altered by domestication and breeding for increased reproductive output.

  • 329. Ericzon, Christina
    et al.
    Pettersson, Jean
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala University.
    Olin, Åke
    Interference from iodide in the determination of trace level selenium1990Inngår i: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 37, nr 7, s. 725-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rate of the reaction between iodide and selenium(IV) at trace levels to form selenium and iodine has been determined in 1–6M hydrochloric acid. The reaction rate increases rapidly with acidity. When hydrochloric acid is added to reduce selenate to selenite prior to the determination of total selenium, some selenium may be lost by reduction to the element if iodide is present. A table of half-lives of the selenite—iodide reaction under various conditions is presented. A method for removal of iodide is suggested.

  • 330.
    Erik, Gioeli
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Utbytesoptimering inom läkemedelsproduktion: Identifiering av kassationsorsaker inom AstraZenecas packningsprocess i Gärtuna2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    The project aimed to deliver recommendations of how to optimize the yield of thepackaging process of tablets and capsules within AstraZeneca's facility in Gärtuna(Södertälje), Sweden. The project scope included nine packaging lines of blisterproducts with highly similar process steps. The crucial part of the puzzle was toidentify cassation sources within these production lines, which was achieved by thecombined methology of qualitative interviews, quantitative surveys and statisticalprocess control applied to logged production data.The following cassation sources were identified:- Cassation as a side effect of start-up controls within an order- Safety cassation of tablets when the blister machine stops- In many cases, the safety cassation also occours when the cartoner stops- A cut-in-half tablet causing cassation of multiple tablets in the rejection steps- Leftover product on the packaging line when the order is finished- Target conflict between high productivity of the production line and high yield withinthe order- Difficulty optimizing machines settings for small order sizes, leading to higher stopfrequency and therefore more safety cassation of tablets, as well as a higher risk thattablets are sorted out in control stepsWhich led to these recommendations:- Optimizing the yield as a target value for process optimization- Log the yield for all the process steps within the packaging line- Consider the possibility of reintroducing rejected blisters containing approvedtablets- Clear prioritization of the target conflict between high productivity and high yield- Analyze if there are any time-consuming steps conflicting with high yield within theprocess of closing an order which are not required to be performed at that particularprocess stepAs well as future work:- Get to the bottom of the correlation between low yield and small order sizes- Investigate further which materials are prone to cause machine stops within thecartoner- Dig deeper into the problem of cut-in-half tablets existing pre-packaging-process

  • 331.
    Eriksson, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bartsch, Maik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergström Lind, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein2013Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, nr SI, s. 105-109Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A recently developed titanium dioxide (TiO2) based on-target method for phosphopeptide enrichment and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS) analysis was used to investigate phosphorylations in the Adenovirus type 2 structural protein pIIIa. Lysates of purified virus particles were separated on 1-D SDS-PAGE and the band for the pIIIa protein was excised for tryptic digestion into peptides that were enriched with the on-target method. The enrichment provided by the method clearly improved the detectability of phosphorylated peptides and the results show for the first time evidence for multi-phosphorylated peptides in pIIIa. Moreover, three novel phosphorylations were identified in the protein sequence, even though the precise positions could not be determined. These results illustrate the potential of the method for the characterization of novel phosphoproteomes in biological samples of medical relevance.

  • 332.
    Eriksson, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Cooperative adsorption behavior of phosphopeptides on TiO2 leads to biased enrichment, detection and quantification2015Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 140, nr 1, s. 303-312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The adsorption behavior of phosphopeptides onto TiO2 surfaces was studied using the quartz crystal microbalance with dissipation monitoring (QCM-D) as the main experimental technique. The main focus is the characterization of the emergence of positive cooperativity under conditions where the peptides have a positively charged C-term. It is shown that when carrying no net charge, small water-soluble peptides as a rule develop positive cooperativity. The impact of the adsorption mechanism on the outcome of TiO2 based enrichment methods was investigated with the help of matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS). The data presented illustrate how the phosphopeptide profile in the enriched material may deviate from that in the native sample, as cooperative phosphopeptides are overrepresented in the former. Furthermore, commonly employed washing and elution solutions may facilitate preferential release of certain peptides, leading to further bias in the recovered sample. Taken together, the results of the present study demonstrate that thorough understanding of the mechanisms behind the adsorption of phosphopeptides on the enrichment material is necessary in order to develop reliable qualitative and quantitative methods for phosphoproteomics.

  • 333.
    Eriksson, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hagfeldt, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique2013Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 7, s. 2019-2025Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2–phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.

  • 334.
    Eriksson, Anna I. K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Enrichment and Separation of Phosphorylated Peptides on Titanium Dioxide Surfaces: Applied and Fundamental Studies2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Protein phosphorylation is a very common posttranslational modification (PTM), which lately has been found to hold the keyrole in the development of many severe diseases, including cancer. Thereby, phosphoprotein analysis tools, generally based on specific enrichment of the phosphoryl group, have been a hot topic during the last decade.

    In this thesis, two new TiO2-based on-target enrichment methods are developed and presented together with enlightening fundamental results.

    Evaluation of the developed methods was performed by the analysis of: custom peptides, β-casein, drinking milk, and the viral protein pIIIa. The results show that: i) by optimizing the enrichment protocol (first method), new phosphorylated peptides can be found and ii) by the addition of a separation step after the enrichment (second method), more multi-phosphorylated peptides, which usually are hard to find, could be detected. The fundamental part, on the other hand, shows that the phosphopeptide adsorption is caused by electrostatic interactions, in general follows the Langmuir model, and the affinity increases with the phosphorylation degree. Here, however, the complexity of the system was also discovered, as the adsorption mechanism was found to be affected by the amino acid sequence of the phosphopeptide.

    Delarbeid
    1. Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide
    Åpne denne publikasjonen i ny fane eller vindu >>Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide
    Vise andre…
    2010 (engelsk)Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, nr 11, s. 4577-4583Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A novel on-target phosphopeptide enrichment method is presented that allows specific enrichment and direct analysis by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS) of phosphorylated peptides. Spots consisting of a thin film of anatase titanium dioxide are sintered onto a conductive glass surface. Enrichment and analysis can be performed on the modified target with minimal sample handling. The protocol leads to an enrichment efficiency that is superior to what has been reported before for similar methods. The method was tested using beta-casein as a model phosphorylated protein as well as with a custom peptide mixed with its phosphorylated form. A very low detection limit, a significantly improved phosphoprofiling capability, and a simple experimental approach provide a powerful tool for the enrichment, detection, and analysis of phosphopeptides.

    HSV kategori
    Forskningsprogram
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-125767 (URN)10.1021/ac100589j (DOI)000278062800040 ()20443553 (PubMedID)
    Tilgjengelig fra: 2010-05-31 Laget: 2010-05-28 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    2. Mesoporous TiO2-Based Experimental Layout for On-Target Enrichment and Separation of Multi- and Monophosphorylated Peptides Prior to Analysis with Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Åpne denne publikasjonen i ny fane eller vindu >>Mesoporous TiO2-Based Experimental Layout for On-Target Enrichment and Separation of Multi- and Monophosphorylated Peptides Prior to Analysis with Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Vise andre…
    2011 (engelsk)Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, nr 3, s. 761-766Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A simple method for on-target enrichment and subsequent separation and analysis of phosphorylated peptides is presented. The tryptic digest of a phosphorylated protein, in this case beta-casein, is loaded onto a spot on a thin stripe made of mesoporous TiO2 sintered onto a conductive glass surface. After washing with a salicylic buffer in order to remove the nonphosphorylated peptides, the stripe is placed in an elution chamber containing a phosphate solution. In a way analogous to thin layer chromatography (TLC), the phosphate solution acts as an eluent, clearly separating multi- and monophosphorylated peptides. By performing matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) along the stripe, the detection of all phosphorylated peptides present in the digest is facilitated, as they are isolated from each other. The method was also tested on commercial drinking milk, achieving successful separation between multi- and monophosphorylated peptides, as well as a detection limit in the femtomole range. As the enrichment, separation, and analysis take place in the same substrate, sample handling and risk of contamination and sample loss is minimized. The results obtained suggest that the method, once optimized, may successfully provide a complete phosphoproteome.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-148662 (URN)10.1021/ac1027879 (DOI)000286689600021 ()21210638 (PubMedID)
    Tilgjengelig fra: 2011-03-09 Laget: 2011-03-09 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    3. Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique
    Åpne denne publikasjonen i ny fane eller vindu >>Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique
    2013 (engelsk)Inngår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, nr 7, s. 2019-2025Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2–phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.

    sted, utgiver, år, opplag, sider
    American Chemical Society (ACS), 2013
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot fysikalisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-195262 (URN)10.1021/jp310161m (DOI)000315432200004 ()
    Tilgjengelig fra: 2013-02-22 Laget: 2013-02-22 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein
    Åpne denne publikasjonen i ny fane eller vindu >>On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein
    Vise andre…
    2013 (engelsk)Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, nr SI, s. 105-109Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A recently developed titanium dioxide (TiO2) based on-target method for phosphopeptide enrichment and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS) analysis was used to investigate phosphorylations in the Adenovirus type 2 structural protein pIIIa. Lysates of purified virus particles were separated on 1-D SDS-PAGE and the band for the pIIIa protein was excised for tryptic digestion into peptides that were enriched with the on-target method. The enrichment provided by the method clearly improved the detectability of phosphorylated peptides and the results show for the first time evidence for multi-phosphorylated peptides in pIIIa. Moreover, three novel phosphorylations were identified in the protein sequence, even though the precise positions could not be determined. These results illustrate the potential of the method for the characterization of novel phosphoproteomes in biological samples of medical relevance.

    Emneord
    Phosphopeptide enrichment, MALDI-MS, Separation, Capsid protein precursor pIIIa, TiO2
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-204683 (URN)10.1016/j.chroma.2013.08.096 (DOI)000327229600012 ()
    Tilgjengelig fra: 2013-08-09 Laget: 2013-08-08 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 335.
    Eriksson, Barbro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Örlefors, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Bergström, Anders
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Positron emission tomography in neuroendocrine tumors1999Inngår i: The Italian Journal of Gastroenterology and Hepatology, ISSN 1125-8055, Vol. 31, s. 167-171Artikkel i tidsskrift (Fagfellevurdert)
  • 336.
    Eriksson, Emma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Determination of trace elements in thrombocytes by ICP-AES2019Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 337.
    Eriksson, Emma
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Production of HIV-1 protease for nuclear magnetic resonance studies2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 338.
    Eriksson, Emma K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Effects of Ubiquinone-10 on the Stability and Mechanical Properties of Lipid Membranes2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Ubiquinones are a group of fat-soluble molecules present in many biological membranes. The most abundant version in humans, ubiquinone-10 (Q10), plays an important role in the mitochondrial respiration chain and also functions as a powerful antioxidant. Accumulating evidence suggests that Q10 also could have other functions in the membrane. The aim of this thesis has been to explore Q10’s possible role as a membrane stabilizer.

    To investigate the potential effect of Q10 in membranes, liposomes with compositions of biological relevance were used as models systems. In lipid systems mimicking that of the inner membrane of the mitochondria, Q10 was found to lower the membrane’s permeability to hydrophilic solutes, render the membrane more resistant to rupturing and promote membrane lipid order. In models mimicking the plasma membrane of E.coli, Q10 was observed to decrease the water permeability and increase the elastic resistance against membrane deformation during osmotic shock. All in all, the results suggest a general membrane stabilizing effect of Q10. The results indicate, however, that the extent of, as well as the mechanisms behind, the membrane stabilizing effects of Q10 vary depending on the membrane lipid composition. Part of the reason for this can likely be traced back to differences in the intermembrane location of Q10.

    Supplementary experiments, which facilitated the investigations of Q10 membrane effects, revealed that the choice of cuvette material was of importance for liposome leakage experiments with fluorescent hydrophilic dyes. The results of these experiments highlight the need to take liposome-cuvette interactions into account when planning and evaluating spectroscopic studies involving liposomes.

    Delarbeid
    1. Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes
    Åpne denne publikasjonen i ny fane eller vindu >>Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes
    2015 (engelsk)Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1848, nr 10, s. 2233-2243Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Abstract Ubiquinone-10 is mostly known for its role as an electron and proton carrier in aerobic cellular respiration and its function as a powerful antioxidant. Accumulating evidence suggest, however, that this well studied membrane component could have several other important functions in living cells. The current study reports on a previously undocumented ability of ubiquinone-10 to modulate the mechanical strength and permeability of lipid membranes. Investigations of DPH fluorescence anisotropy, spontaneous and surfactant induced leakage of carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces were used to probe the effects caused by inclusion of ubiquinone-10 in the membrane of phospholipid liposomes. The results show that ubiquinone in concentrations as low as 2 mol.% increases the lipid packing order and condenses the membrane. The altered physicochemical properties result in a slower rate of release of hydrophilic components, and render the membrane more resistant towards rupture. As judged from comparative experiments using the polyisoprenoid alcohol solanesol, the quinone moiety is essential for the membrane stabilizing effects to occur. Our findings imply that the influence of ubiquinone-10 on the permeability and mechanical properties of phospholipid membranes is similar to that of cholesterol. The reported data indicate, however, that the molecular mechanisms are different in the two cases.

    Emneord
    Coenzyme Q10, Liposomes, Leakage, Membrane stability, Solanesol
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-253627 (URN)10.1016/j.bbamem.2015.05.002 (DOI)000362153400032 ()
    Forskningsfinansiär
    Swedish Research Council, 621-2011-3524Swedish Cancer Society, CAN20111504
    Tilgjengelig fra: 2015-05-29 Laget: 2015-05-29 Sist oppdatert: 2018-09-23bibliografisk kontrollert
    2. Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.
    2018 (engelsk)Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1860, nr 5, s. 1205-1215Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing function. In line with this, we showed in a previous study that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) membranes. In the current study we report on the effects exerted by Q10 in membranes having a more complex lipid composition designed to mimic that of the inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and permeability measurements, as well as investigations probing the interaction of liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10 also in the IMM-mimicking membranes. Comparative investigations examining the effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on membranes composed of individual IMM components suggest, moreover, that Q10 improves the membrane barrier properties via different mechanisms depending on the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on CF release from pure POPC membranes appears to be directly and solely related to Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability to amplify intrinsic curvature elastic stress dominates in case of membranes containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE).

    Emneord
    Biomimetic membranes, Coenzyme Q10, Liposomes, Membrane stability, Solanesol
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-353473 (URN)10.1016/j.bbamem.2018.02.015 (DOI)000435057700029 ()29470946 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 2016-03464Swedish Cancer Society, 17 0566
    Tilgjengelig fra: 2018-06-13 Laget: 2018-06-13 Sist oppdatert: 2018-09-23bibliografisk kontrollert
    3. Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane
    Åpne denne publikasjonen i ny fane eller vindu >>Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane
    Vise andre…
    2019 (engelsk)Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1861, nr 7, s. 1388-1396Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Bacteria need to be able to adapt to sudden changes in their environment, including drastic changes in the surrounding osmolarity. As part of this adaptation, the cells adjust the composition of their cytoplasmic membrane. Recent studies have shown that ubiquinones, lipid soluble molecules involved in cell respiration, are overproduced by bacteria grown in hyperosmotic conditions and it is thus believed that these molecules can provide with osmoprotection. Hereby we explore the mechanisms behind these observations. Liposomes with a lipid headgroup composition mimicking that of the cytoplasmic membrane of E. coli are used as suitable models. The effect of ubiquinone-10 (Q10) on water transport across the membranes is characterized using a custom developed fluorescence-based experimental approach to simultaneously determine the membrane permeability coefficient and estimate the elastic resistance of the membrane towards deformation. It is shown that both parameters are affected by the presence of ubiquinone-10. Solanesol, a molecule similar to Q10 but lacking the quinone headgroup, also provides with osmoprotection although it only improves the resistance of the membrane against deformation. The fluorescence experiments are complemented by cryogenic transmission electron microscopy studies showing that the E. coli membrane mimics tend to flatten into spheroid oblate structures when osmotically stressed, suggesting the possibility of lipid segregation. In agreement with its proposed osmoprotective role, the flattening process is hindered by the presence of Q10.

    Emneord
    Coenzyme Q10, Liposomes, Membrane elasticity, Osmotic stress, Solanesol, Water permeability
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot fysikalisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-361360 (URN)10.1016/j.bbamem.2019.04.008 (DOI)000474325100012 ()31026443 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 2016-03464Swedish Cancer Society, 17 0566
    Tilgjengelig fra: 2018-09-23 Laget: 2018-09-23 Sist oppdatert: 2020-02-07bibliografisk kontrollert
    4. Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.
    Åpne denne publikasjonen i ny fane eller vindu >>Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.
    2018 (engelsk)Inngår i: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 215, s. 63-70, artikkel-id S0009-3084(18)30129-4Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.

    Emneord
    Carboxyfluorescein, Fluorescence, Polystyrene cuvettes, QCM-D, Quartz cuvettes, Spontaneous leakage
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-357926 (URN)10.1016/j.chemphyslip.2018.07.006 (DOI)000443661800008 ()30076799 (PubMedID)
    Tilgjengelig fra: 2018-08-22 Laget: 2018-08-22 Sist oppdatert: 2018-11-08bibliografisk kontrollert
  • 339.
    Eriksson, Emma K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Agmo Hernandez, Victor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.2018Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1860, nr 5, s. 1205-1215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing function. In line with this, we showed in a previous study that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) membranes. In the current study we report on the effects exerted by Q10 in membranes having a more complex lipid composition designed to mimic that of the inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and permeability measurements, as well as investigations probing the interaction of liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10 also in the IMM-mimicking membranes. Comparative investigations examining the effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on membranes composed of individual IMM components suggest, moreover, that Q10 improves the membrane barrier properties via different mechanisms depending on the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on CF release from pure POPC membranes appears to be directly and solely related to Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability to amplify intrinsic curvature elastic stress dominates in case of membranes containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE).

  • 340.
    Eriksson, Emma K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.2018Inngår i: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 215, s. 63-70, artikkel-id S0009-3084(18)30129-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.

  • 341.
    Eriksson, Emma K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Edwards, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grad, Philipp
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Gedda, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Agmo Hernández, Víctor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane2019Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1861, nr 7, s. 1388-1396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bacteria need to be able to adapt to sudden changes in their environment, including drastic changes in the surrounding osmolarity. As part of this adaptation, the cells adjust the composition of their cytoplasmic membrane. Recent studies have shown that ubiquinones, lipid soluble molecules involved in cell respiration, are overproduced by bacteria grown in hyperosmotic conditions and it is thus believed that these molecules can provide with osmoprotection. Hereby we explore the mechanisms behind these observations. Liposomes with a lipid headgroup composition mimicking that of the cytoplasmic membrane of E. coli are used as suitable models. The effect of ubiquinone-10 (Q10) on water transport across the membranes is characterized using a custom developed fluorescence-based experimental approach to simultaneously determine the membrane permeability coefficient and estimate the elastic resistance of the membrane towards deformation. It is shown that both parameters are affected by the presence of ubiquinone-10. Solanesol, a molecule similar to Q10 but lacking the quinone headgroup, also provides with osmoprotection although it only improves the resistance of the membrane against deformation. The fluorescence experiments are complemented by cryogenic transmission electron microscopy studies showing that the E. coli membrane mimics tend to flatten into spheroid oblate structures when osmotically stressed, suggesting the possibility of lipid segregation. In agreement with its proposed osmoprotective role, the flattening process is hindered by the presence of Q10.

  • 342.
    Eriksson, Louise
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Method development and optimization for determination of lipid oxidation in emulsions2016Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Lipid emulsions in parenteral nutrition’s consist of two immiscible liquids described as oil in water phase. The oils in the emulsions can start to oxidize and make it become rancid. The oxidation can be measured for peroxide value, anisidine value and for free fatty acids (FFAs) as primary- and secondary oxidation products.

    This master thesis presents an analytical method used for analysis of oxidation products. The aim of this project was to come up with a method to separate the oil from the water-phase, to a sufficient yield and as pure as possible for analysis in a spectrophotometer called FoodLab fat. During the way experiments regarding stability of oils and finally a stability study on emulsions were done.

    Starting the separation experiments with ethanol to break the emulsion, this turned out to be the best way to go. Further investigation through extractions with 2- propanol/isooctane and ethanol/heptane were tested. The method needed to be simple, easy to use and not too time-consuming but still be repeatable and reliable.

    To optimize the separation, different centrifugation volumes, forces and times were tested. The results showed that in order to get the best separation the centrifugation volume and force cannot be too large or too small.

    The final method proved to be successful for the use as research method and to be able to see trends of oxidation for the products. Further research and validation of the instrument and the method needs to be done before it can be used as a quality control method. 

  • 343.
    Eriksson, Malin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    The Establishment of a Small Challenger Company in a Segmented High-Technology Life Science Market: Challenges and Opportunities - a Model Case Study2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

     This study aims to identify the challenges and opportunities of a small challenger

    company in a rigid and conservative high technology life science market. Strategies

    for finding a foothold, establish a position and creating a viable company is

    discussed. Qualitative and quantitative data was collected through interviews,

    online survey and conjoint analysis which were used as market research tools. For

    an entrepreneurial firm in the life science market it is important to tend to their most

    valuable resource, the employees, and it is vital that they have an extensive

    knowledge of the market that they are active in. Strategic planning tools and

    templates aid in executing and implementing the proposed business model.

    Recommendations for a model case entrepreneurial company regarding continued

    market research, increasing sales and strategies for marketing are made. Included

    in the thesis is also a discussion of wall effects in HPLC and ways to counteract

    them.

  • 344.
    Eriksson, Olle
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Olsson, Ulf
    Swedish Univ Agr Sci, Unit Appl Stat & Math, Uppsala, Sweden..
    Marteinsdottir, Ina
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Holstad, Maria
    Univ Uppsala Hosp, Dept Neurosci, Psychiat Unit, Uppsala, Sweden..
    Ågren, Hans
    Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Hartvig, Per
    Univ Copenhagen, Dept Drug Design & Pharmacol, Copenhagen, Denmark..
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Naessén, Tord
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 9, artikkel-id e0159538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Study Objective To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. Background Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. Methods Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". Results There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (pre-menstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (r(s) = -0.635; 0.027). The control group showed no such correlation. Conclusion Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.

  • 345.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Carlsson, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Blom, Elisabeth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Velikyan, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation2012Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, nr 3, s. 415-421Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Islet transplantation is a promising treatment for type 1 diabetes mellitus, but the fate of the cells after intraportal infusion is unclear. It is therefore imperative to develop novel techniques for noninvasive imaging and quantification of events following islet transplantation.

    METHODS:

    Small islet-like microbeads, avidin-covered agarose resins (AARs), were used as a model system for islet transplantation. Capability for specific [(68)Ga]Ga-DOTA-(PEG)(2)-biotin uptake and retention for either AARs or human islets conjugated with avidin by means of a heparin scaffold was studied in vitro. Biodistribution of the novel positron emission tomography (PET) tracer [(68)Ga]Ga-DOTA-(PEG)(2)-biotin was evaluated in mice treated by intraportal transplantation of AARs by μPET/computed tomography and ex vivo organ distribution and compared with control mice.

    RESULTS:

    AARs had high capability to bind [(68)Ga]Ga-DOTA-(PEG)(2)-biotin, close to 50% of administrated tracer/μl in vitro (>0.25 MBq/μl). Avidin-tagged human islets could bind on average 2.2% of administered tracer/μl. Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by preadministration of unlabeled biotin.

    CONCLUSIONS:

    Avidin-tagged islet-like objects can be tracked in hepatic volume after intraportal transplantation by using [(68)Ga]Ga-DOTA-(PEG)(2)-biotin and PET.

  • 346.
    Eriksson, Oskar
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Ramström, Margareta
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Hörnaeus, Katarina
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Bergquist, Jonas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mokhtari, Dariush
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Siegbahn, Agneta
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    The Eph Tyrosine Kinase Receptors EphB2 and EphA2 Are Novel Proteolytic Substrates of Tissue Factor/Coagulation Factor VIIa2014Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, nr 47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tissue factor (TF) binds the serine protease factor VIIa (FVIIa) to form a proteolytically active complex that can trigger coagulation or activate cell signaling. Here we addressed the involvement of tyrosine kinase receptors (RTKs) in TF/FVIIa signaling by antibody array analysis and subsequently found that EphB2 and EphA2 of the Eph RTK family were cleaved in their ectodomains by TF/FVIIa. We used N-terminal Edman sequencing and LC-MS/MS analysis to characterize the cleaved Eph isoforms and identified a key arginine residue at the cleavage site, in agreement with the tryptic serine protease activity of FVIIa. Protease-activated receptor 2 (PAR2) signaling and downstream coagulation activity was non-essential in this context, in further support of a direct cleavage by TF/FVIIa. EphB2 was cleaved by FVIIa concentrations in the subnanomolar range in a number of TF expressing cell types, indicating that the active cellular pool of TF was involved. FVIIa caused potentiation of cell repulsion by the EphB2 ligand ephrin-B1, demonstrating a novel proteolytical event to control Eph-mediated cell segregation. These results define Eph RTKs as novel proteolytical targets of TF/FVIIa and provide new insights into how TF/FVIIa regulates cellular functions independently of PAR2.

  • 347.
    Eriksson, Susanna K
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Hahlin, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Molekyl- och kondenserade materiens fysik.
    Kahk, Juhan Matthias
    Villar-Garcia, Ignacio J
    Webb, Matthew J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Yakimova, Rositza
    Rensmo, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Molekyl- och kondenserade materiens fysik.
    Edström, Kristina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Hagfeldt, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Siegbahn, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Molekyl- och kondenserade materiens fysik.
    Edwards, Mårten O M
    Karlsson, Patrik G
    Backlund, Klas
    Ahlund, John
    Payne, David J
    A versatile photoelectron spectrometer for pressures up to 30 mbar2014Inngår i: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 85, nr 7, s. 075119-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High-pressure photoelectron spectroscopy is a rapidly developing technique with applications in a wide range of fields ranging from fundamental surface science and catalysis to energy materials, environmental science, and biology. At present the majority of the high-pressure photoelectron spectrometers are situated at synchrotron end stations, but recently a small number of laboratory-based setups have also emerged. In this paper we discuss the design and performance of a new laboratory based high pressure photoelectron spectrometer equipped with an Al Kα X-ray anode and a hemispherical electron energy analyzer combined with a differentially pumped electrostatic lens. The instrument is demonstrated to be capable of measuring core level spectra at pressures up to 30 mbar. Moreover, valence band spectra of a silver sample as well as a carbon-coated surface (graphene) recorded under a 2 mbar nitrogen atmosphere are presented, demonstrating the versatility of this laboratory-based spectrometer.

  • 348.
    Eriksson, Tor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Synthesis of 2-(ethoxy(hydroxy)phosphoryl)-3-phenylpropyl ethanethioate2019Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 349.
    Euerby, Melvin R.
    et al.
    Hichrom Ltd, Reading, Berks, England.;Univ Strathclyde, Glasgow, Lanark, Scotland.;Open Univ, Milton Keynes, Bucks, England..
    Fever, Mark
    Hichrom Ltd, Reading, Berks, England..
    Hulse, Jennifer
    Hichrom Ltd, Reading, Berks, England..
    James, Matthew
    Hichrom Ltd, Reading, Berks, England..
    Petersson, Patrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Novo Nordisk AS, Bagsvaerd, Denmark..
    Pipe, Cohn
    Hichrom Ltd, Reading, Berks, England..
    Maximization of Selectivity in Reversed-Phase Liquid Chromatographic Method Development Strategies2017Inngår i: LC GC North America, ISSN 1527-5949, E-ISSN 1939-1889, Vol. 35, nr 4, s. 258-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The selectivity of different combinations.of organic modifiers, pH, and types of reversed-phase liquid chromatography (LC) materials has been characterized using Tanaka column characterization, linear solvent energy relationships (LSER), and selectivity correlations. The three characterization techniques highlighted the potential complementary selectivity of these phases and conditions as well as the type and dominancy of some of the retention mechanisms involved. Subsequently, selectivity differences were proven to be valid in the practical separation of acids, bases, and neutral analytes. This paper aims to help chromatographers to produce highly efficient method development strategies for reversed phase LC separations in a relatively short time frame.

  • 350.
    Fabini, Edoardo
    et al.
    Univ Bologna, Dept Pharm & Biotechnol, Via Belmeloro 6, I-40126 Bologna, Italy..
    Danielson, U. Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology2017Inngår i: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 144, s. 188-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many molecules fail to reach the market due to poor pharmacokinetic (PK) properties, rendering the potential drug virtually unavailable for the primary target despite efficient administration to the body. PK properties of endogenous and exogenous compounds in mammals are dependent, among other factors, on their ability to interact with serum proteins. The extent of binding can greatly influence their ADME (adsorption, distribution, metabolism and execration) profile. Reliable and cost-effective bioavailability studies, early in the drug discovery process, can lead to an improvement of the success rate for compounds entering clinical trials. Optical biosensors based on surface plasmon resonance (SPR) detection emerged as an efficient approach to obtain large amounts of information about the binding of small molecules to serum proteins. Simple, automated and fast assays provide a good throughput, versatility and highly informative data output, rendering the methodology particularly suited for early screening. The ability to provide basic information on PK can be easily coupled to structure-activity relationship analysis. In this review, features of the technology and its employment for the study of serum protein-small molecule interactions are presented and discussed. 

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  • asciidoc
  • rtf