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  • 351.
    Tiinus, My
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Utvärdering av substrat för biogasproduktion2013Independent thesis Basic level (degree of Bachelor), 10,5 poäng / 16 hpOppgave
    Abstract [en]

    The purpose of this study was to evaluate the different substrates that enter the digestion on Sundet wastewater treatment plant for production of biogas.

    This work have done an analysis of data about the biogasproduction from January 2012 to feburari 2013, this showed that the food substrates has a greater gas production than internal sludge.

    Through laboratory test the VS, TS and COD values for all the substrates used in the biogas production could be determinded. But the COD-method was less optimal for analysis of fat and food, therefore it optimized the method for fat but due to time constraints, this could not be done on the food substrates.

  • 352.
    Tollstoy Tegler, Lotta
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan. MIT, MA 02139 USA.
    Corin, Karolina
    MIT, MA 02139 USA; University of Witwatersrand, South Africa; University of Witwatersrand, South Africa.
    Hillger, Julia
    MIT, MA 02139 USA.
    Wassie, Brooke
    MIT, MA 02139 USA.
    Yu, Yanmei
    MIT, MA 02139 USA; Sichuan University, Peoples R China.
    Zhang, Shuguang
    MIT, MA 02139 USA.
    Cell-free expression, purification, and ligand-binding analysis of Drosophila melanogaster olfactory receptors DmOR67a, DmOR85b and DmORCO2015Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, nr 7867Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insects transmit numerous devastating diseases, including malaria, dengue fever, and sleeping sickness. Olfactory cues guide insects to their hosts, and are thus responsible for disease transmission. Understanding the molecular basis of insect olfaction could facilitate the development of interventions. The first step is to heterologously overexpress and purify insect olfactory receptors (ORs). This is challenging, as ORs are membrane proteins. Here, we show that insect ORs and their co-receptor can be expressed in an E. coli cell-free system. After immunoaffinity chromatography, the ORs are similar to 95% pure, and up to 1 mg/10 ml reaction is obtained. Circular dichroism together with microscale thermophoresis indicate that each receptor is properly folded, and can bind its respective ligand. This is the first time insect ORs have been expressed in an E. coli system. The methods described here could facilitate future structure-function studies, which may aid in developments to alleviate the suffering of millions caused by insect-transmitted diseases.

  • 353.
    Tu, William B.
    et al.
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Helander, Sara
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Pilstål, Robert
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Ashley Hickman, K.
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Lourenco, Corey
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Jurisica, Igor
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Raught, Brian
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Penn, Linda Z.
    University of Toronto, Canada; Princess Margaret Cancer Centre, Canada.
    Myc and its interactors take shape2015Inngår i: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms, ISSN 1874-9399, E-ISSN 1876-4320, Vol. 1849, nr 5, s. 469-483Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The Myc oncoprotein is a key contributor to the development of many human cancers. As such, understanding its molecular activities and biological functions has been a field of active research since its discovery more than three decades ago. Genome-wide studies have revealed Myc to be a global regulator of gene expression. The identification of its DNA-binding partner protein, Max, launched an area of extensive research into both the protein-protein interactions and protein structure of Myc. In this review, we highlight key insights with respect to Myc interactors and protein structure that contribute to the understanding of Mycs roles in transcriptional regulation and cancer. Structural analyses of Myc show many critical regions with transient structures that mediate protein interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF-b, provide mechanistic insight into Mycs transcriptional activities, while others, such as ubiquitin ligases, regulate the Myc protein itself. It is appreciated that Myc possesses a large interactome, yet the functional relevance of many interactors remains unknown. Here, we discuss future research trends that embrace advances in genome-wide and proteome-wide approaches to systematically elucidate mechanisms of Myc action. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology. (C) 2014 Elsevier B.V. All rights reserved.

  • 354.
    Ullsten, Sara
    et al.
    Uppsala University, Sweden.
    Bohman, Sara
    Uppsala University, Sweden.
    Oskarsson, Marie E.
    Uppsala University, Sweden.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Westermark, Gunilla T.
    Uppsala University, Sweden.
    Carlsson, Per-Ola
    Uppsala University, Sweden.
    Islet amyloid deposits preferentially in the highly functional and most blood-perfused islets2017Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 6, nr 7, s. 458-468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Islet amyloid and beta cell death in type 2 diabetes are heterogeneous events, where some islets are affected early in the disease process, whereas others remain visibly unaffected. This study investigated the possibility that inter-islet functional and vascular differences may explain the propensity for amyloid accumulation in certain islets. Highly blood-perfused islets were identified by microspheres in human islet amyloid polypeptide expressing mice fed a high-fat diet for three or 10 months. These highly blood-perfused islets had better glucose-stimulated insulin secretion capacity than other islets and developed more amyloid deposits after 10 months of high-fat diet. Similarly, human islets with a superior release capacity formed more amyloid in high glucose culture than islets with a lower release capacity. The amyloid formation in mouse islets was associated with a higher amount of prohormone convertase 1/3 and with a decreased expression of its inhibitor proSAAS when compared to islets with less amyloid. In contrast, levels of prohormone convertase 2 and expression of its inhibitor neuroendocrine protein 7B2 were unaltered. A misbalance in prohormone convertase levels may interrupt the normal processing of islet amyloid polypeptide and induce amyloid formation. Preferential amyloid load in the most blood-perfused and functional islets may accelerate the progression of type 2 diabetes.

  • 355.
    Ulrich, Jason D.
    et al.
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Ulland, Tyler K.
    Washington Univ, MO 63130 USA.
    Mahan, Thomas E.
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Song, Wilbur M.
    Washington Univ, MO 63130 USA.
    Zhou, Yingyue
    Washington Univ, MO 63130 USA.
    Reinartz, Mariska
    Washington Univ, MO 63110 USA; Radboud Univ Nijmegen, Netherlands.
    Choi, Seulah
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Jiang, Hong
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Stewart, Floy R.
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Anderson, Elise
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    Wang, Yaming
    Washington Univ, MO 63130 USA; Eli Lilly and Co, IN 46285 USA.
    Colonna, Marco
    Washington Univ, MO 63130 USA.
    Holtzman, David M.
    Washington Univ, MO 63110 USA; Washington Univ, MO 63130 USA; Washington Univ, MO 63130 USA.
    ApoE facilitates the microglial response to amyloid plaque pathology2018Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 215, nr 4, s. 1047-1058Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One of the hallmarks of Alzheimers disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (A beta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric A beta in the brain. In addition to influencing A beta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1 Delta E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct A beta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

  • 356.
    Urbancic, Dunja
    et al.
    Univ Ljubljana, Slovenia.
    Kotar, Anita
    Slovenian NMR Ctr, Slovenia.
    Smid, Alenka
    Univ Ljubljana, Slovenia.
    Jukic, Marko
    Univ Ljubljana, Slovenia.
    Gobec, Stanislav
    Univ Ljubljana, Slovenia.
    Mårtensson, Lars-Göran
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Plavec, Janez
    Slovenian NMR Ctr, Slovenia.
    Mlinaric-Rascan, Irena
    Univ Ljubljana, Slovenia.
    Methylation of selenocysteine catalysed by thiopurine S-methyltransferase2019Inngår i: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1863, nr 1, s. 182-190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Methylation driven by thiopurine S-methylatransferase (TPMT) is crucial for deactivation of cytostatic and immunosuppressant thiopurines. Despite its remarkable integration into clinical practice, the endogenous function of TPMT is unknown. Methods: To address the role of TPMT in methylation of selenium compounds, we established the research on saturation transfer difference (STD) and Se-77 NMR spectroscopy, fluorescence measurements, as well as computational molecular docking simulations. Results: Using STD NMR spectroscopy and fluorescence measurements of tryptophan residues in TPMT, we determined the binding of selenocysteine (Sec) to human recombinant TPMT. By comparing binding characteristics of Sec in the absence and in the presence of methyl donor, we confirmed S-adenosylmethionine (SAM)-induced conformational changes in TPMT. Molecular docking analysis positioned Sec into the active site of TPMT with orientation relevant for methylation reaction. Se-methylselenocysteine (MeSec), produced in the enzymatic reaction, was detected by Se-77 NMR spectroscopy. A direct interaction between Sec and SAM in the active site of rTPMT and the formation of both products, MeSec and S-adenosylhomocysteine, was demonstrated using NMR spectroscopy. Conclusions: The present study provides evidence on in vitro methylation of Sec by rTPMT in a SAM-dependant manner. General significance: Our results suggest novel role of TPMT and demonstrate new insights into enzymatic modifications of the 21st amino acid.

  • 357.
    Usmani, Shariq M.
    et al.
    Ulm University Medical Center, Germany .
    Zirafi, Onofrio
    Ulm University Medical Center, Germany .
    Mueller, Janis A.
    Ulm University Medical Center, Germany .
    Sandi-Monroy, Nathallie L.
    Ulm University Medical Center; Kinderwunsch-Zentrum Ulm, Germany.
    Yadav, Jay K.
    Ulm University, Germany.
    Meier, Christoph
    Ulm University, Germany .
    Weil, Tanja
    Ulm University, Germany.
    Roan, Nadia R.
    University of California at San Francisco, USA .
    Greene, Warner C.
    University of California at San Francisco, USA.
    Walther, Paul
    Ulm University, Germany.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Wetzel, Ronald
    University of Pittsburgh, PA, USA .
    Pilcher, Christopher D.
    University of California, San Francisco, USA .
    Gagsteiger, Friedrich
    Kinderwunsch-Zentrum Ulm, Germany.
    Fändrich, Marcus
    Ulm University, Germany.
    Kirchhoff, Frank
    Ulm University Medical Center, Germany.
    Münch, Jan
    Ulm University Medical Center, Germany.
    Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen2014Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, s. 3508-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Naturally occurring fragments of the abundant semen proteins prostatic acid phosphatase ( PAP) and semenogelins form amyloid fibrils in vitro. These fibrils boost HIV infection and may play a key role in the spread of the AIDS pandemic. However, the presence of amyloid fibrils in semen remained to be demonstrated. Here, we use state of the art confocal and electron microscopy techniques for direct imaging of amyloid fibrils in human ejaculates. We detect amyloid aggregates in all semen samples and find that they partially consist of PAP fragments, interact with HIV particles and increase viral infectivity. Our results establish semen as a body fluid that naturally contains amyloid fibrils that are exploited by HIV to promote its sexual transmission.

  • 358.
    Vagin, Mikhail
    et al.
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Wannapob, Rodtichoti
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten. Prince Songkla University, Thailand.
    Liu, Yu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Sichuan Agriculture University, Peoples R China.
    Mak, Wing Cheung
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Potential-modulated Electrocapacitive Properties of Soft Microstructured Polypyrrole2017Inngår i: Electroanalysis, ISSN 1040-0397, E-ISSN 1521-4109, Vol. 29, nr 1, s. 203-207Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Microstructured materials are becoming important for high performance electrochemical device especially for energy storage due to their advantageous diffusion and flux properties. Utilizing a rationally designed hollow structured polypyrrole microparticles (PPyMPs) with controllable wall thicknesses of -110 to 340 nm, we observed a significant morphological effect on electrocapacitive kinetics of the PPyMPs modulated by the voltammetric potential window and scan rate. The thinhollow architecture of PPyMPs revealed significant enhancement of charge storage performance (up to 447%), high retention at high scan rate and faster charge/dis-charge kinetics compared to the thick-hollow PPyMPs due to the larger accessible surface area and decrease of diffusion length. These findings demonstrated the electrocapacitive kinetics performance of microstructured soft materials related to morphological effect modulated by operational conditions. Our study provides new insight on electrochemistry of soft electrode materials with controlled nanostructured morphology for understanding the mechanism of charge insertion and mass diffusion for the future development of high performance porous electrode material.

  • 359.
    Vikingsson, Svante
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Gréen, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping Sweden.
    Brinkhagen, Linda
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping Sweden.
    Mukhtar, Shahzabe
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping Sweden.
    Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry.2016Inngår i: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 8, nr 9, s. 950-956Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright © 2015 John Wiley & Sons, Ltd.

  • 360.
    Vikingsson, Svante
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Identification of AKB-48 and 5F-AKB-48 Metabolites in Authentic Human Urine Samples Using Human Liver Microsomes and Time of Flight Mass Spectrometry2015Inngår i: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 39, nr 6, s. 426-435Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The occurrence of structurally related synthetic cannabinoids makes the identification of unique markers of drug intake particularly challenging. The aim of this study was to identify unique and abundant metabolites of AKB-48 and 5F-AKB-48 for toxicological screening in urine. Investigations of authentic urine samples from forensic cases in combination with human liver microsome (HLM) experiments were used for identification of metabolites. HLM incubations of AKB-48 and 5F-AKB-48 along with 35 urine samples from authentic cases were analyzed with liquid chromatography quadrupole tandem time of flight mass spectrometry. Using HLMs 41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 were identified, principally represented by hydroxylation but also ketone formation and dealkylation. Monohydroxylated metabolites were replaced by di- and trihydroxylated metabolites within 30 min. The metabolites from the HLM incubations accounted for on average 84% (range, 67-100) and 91% (range, 71-100) of the combined area in the case samples for AKB-48 and 5F-AKB-48, respectively. While defluorinated metabolites accounted for on average 74% of the combined area after a 5F-AKB-48 intake only a few identified metabolites were shared between AKB-48 and 5F-AKB-48, illustrating the need for a systematic approach to identify unique metabolites. HLMs in combination with case samples seem suitable for this purpose.

  • 361.
    Vikingsson, Svante
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Wohlfarth, Ariane
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Andersson, Mikael
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Roman, Markus
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kronstrand, Robert
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Identifying Metabolites of Meclonazepam by High-Resolution Mass Spectrometry Using Human Liver Microsomes, Hepatocytes, a Mouse Model, and Authentic Urine Samples2017Inngår i: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 19, nr 3, s. 736-742Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Meclonazepam is a benzodiazepine patented in 1977 to treat parasitic worms, which recently appeared as a designer benzodiazepine and drug of abuse. The aim of this study was to identify metabolites suitable as biomarkers of drug intake in urine using high-resolution mass spectrometry, authentic urine samples, and different model systems including human liver microsomes, cryopreserved hepatocytes, and a mice model. The main metabolites of meclonazepam found in human urine were amino-meclonazepam and acetamido-meclonazepam; also, minor peaks for meclonazepam were observed in three of four urine samples. These observations are consistent with meclonazepam having a metabolism similar to that of other nitro containing benzodiazepines such as clonazepam, flunitrazepam, and nitrazepam. Both metabolites were produced by the hepatocytes and in the mice model, but the human liver microsomes were only capable of producing minor amounts of the amino metabolite. However, under nitrogen, the amount of amino-meclonazepam produced increased 140 times. This study comprehensively elucidated meclonazepam metabolism and also illustrates that careful selection of in vitro model systems for drug metabolism is needed, always taking into account the expected metabolism of the tested drug.

  • 362.
    Vikström, Elena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Bui, Lan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Role of calcium signalling and phosphorylations in disruption of the epithelial junctions by Pseudomonas aeruginosa quorum sensing molecule2010Inngår i: European Journal of Cell Biology, ISSN 0171-9335, E-ISSN 1618-1298, Vol. 89, nr 8, s. 584-597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Pseudomonas aeruginosa. cell-cell communication based on acyl-homoserine lactone (HSL) quorum sensing molecules is known to coordinate the production of virulence factors and biofilms by the bacterium. Incidentally, these bacterial signals can also modulate mammalian cell behaviour. We demonstrate here that 3O-C-12-HSL can induce changes in calcium signalling through influx and release of calcium from thapsigargin-sensitive stores and delocalization of inositol 1,4,5-trisphosphate receptors (IP3R), but not of ryanodine receptors (RyR). In parallel, P. aeruginosa 3O-C-12-HSL disrupts junctions in human Caco-2 cells as evidenced by a reduction of the expression and distribution of ZO-3 and JAM-A. Using co-immunoprecipitation we also found an alteration in the binding of ZO-3 to JAM-A in protein complexes. Moreover, 3O-C-12-HSL-treatment resulted in tyrosine hyperphosphorylation of ZO-3 and JAM-A. On the contrary, serine and threonine residues of ZO-1 and JAM-A became less phosphorylated after exposition of 3O-C-12-HSL. The 3O-C-12-HSL-induced intracellular calcium signalling and alteration in the phosphorylation status of junction proteins furthermore correlated with changes in the association between JAM-A-ZO-3. The calcium inhibitors thapsigargin, xestospongin C. and dantrolene partly prevented the 3O-C-12-HSL-induced decreases in TER and increases in the paracellular flux of 10 kDa dextran. These findings clearly suggest that P. aeruginosa 3O-C-12-HSL can cause the loss of epithelial barrier function via calcium signalling and further alteration in the phosphorylation status of junction proteins; and that bacterial quorum sensing signals represent inter-kingdom signalling.

  • 363.
    Vikström, Elena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Bui, Lan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    The junctional integrity of epithelial cells is modulated by Pseudomonas aeruginosa quorum sensing molecule through phosphorylation-dependent mechanisms2009Inngår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 315, nr 2, s. 313-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Pseudomonas aeruginosa, cell-cell Communication based on acyl-homoserine lactone (HSL) quorum sensing molecules is known to coordinate the production of virulence factors and biofilms by the bacterium. Incidentally, these bacterial signals can also modulate mammalian cell behaviour. We report that 3O-C-12-HSL can disrupt adherens junctions in human epithelial Caco-2 cells as evidenced by a reduction of the expression and distribution of E-cadherin and beta-catenin. Using co-immunoprecipitation we also found that P. aeruginosa 3O-C-12-HSL-treatment resulted in tyrosine hyperphosphorylation of E-cadherin, beta-catenin, occludin and ZO-1. Similarly, serine and threonine residues of E-cadherin and ZO-1 became more phosphorylated after 3O-C-12-HSL treatment. On the contrary, occludin and beta-catenin underwent dephosphorylation on serine and threonine residues after exposition of 3O-C-12-HSL. These changes in the phosphorylation state were paralleled by alteration in the Structure of junction complexes and increased paracellular permeability. Moreover, pre-treatment of the Caco-2 cells with protein phosphatase and kinase inhibitors prevented 3O-C-12-HSL-induced changes in paracellular permeability and interactions between occludin-ZO-1 and the E-cadherin-beta-catenin. These findings clearly suggest that an alteration in the phosphorylation status of junction proteins are involved in the changes in cell junction associations and enhanced paracellular permeability, and that bacterial signals are indeed sensed by the host cells.

  • 364.
    Villamil Giraldo, Ana M.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Appelqvist, Hanna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Ederth, Thomas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death2014Inngår i: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, s. 1460-1464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lysosomes are acidic organelles essential for degradation, signalling and cell homoeostasis. In addition, they play a key role in cell death. Permeabilization of the lysosomal membrane and release of hydrolytic enzymes to the cytosol accompanies apoptosis signalling in several systems. The regulatory mechanism of lysosomal stability is, however, poorly understood. Lipophilic or amphiphilic compounds with a basic moiety will become protonated and trapped within lysosomes, and such lysosomotropic behaviour is also found in many pharmacological drugs. The natural sphingolipid sphingosine exhibits lysosomotropic detergent ability and is an endogenous candidate for controlling lysosomal membrane permeabilization. The lysosomotropic properties of certain detergents might be of use in lysosome-targeting anticancer drugs and drug delivery system in the future. The present review summarizes the current knowledge on the targeting and permeabilizing properties of lysosomotropic detergents from a cellular and physicochemical perspective.

  • 365.
    Villamil Giraldo, Ana Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fyrner, Timmy
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Wennmalm, Stefan
    Royal Institute Technology, Sweden.
    Parikh, Atul N.
    University of Calif Davis, CA 95616 USA; University of Calif Davis, CA 95616 USA.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Ederth, Thomas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Spontaneous Vesiculation and pH-Induced Disassembly of a Lysosomotropic Detergent: Impacts on Lysosomotropism and Lysosomal Delivery2016Inngår i: LANGMUIR, ISSN 0743-7463, Vol. 32, nr 50, s. 13566-13575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lysosomotropic detergents (LDs) selectively rupture lysosomal membranes through mechanisms that have yet to be characterized. A consensus view, currently, holds that LDs, which are weakly basic, diffuse across cellular membranes as monomers in an uncharged state, and via protonation in the acidic lysosomal compartment, they become trapped, accumulate, and subsequently solubilize the membrane and induce lysosomal membrane permeabilization. Here we demonstrate that the lysosomotropic detergent O-methyl-serine dodecylamide hydrochloride (MSDH) spontaneously assembles into vesicles at, and above, cytosolic pH, and that the vesicles disassemble as the pH reaches 6.4 or lower. The aggregation commences at concentrations below the range of those used in cell studies. Assembly and disassembly of the vesicles was studied via dynamic light scattering, zeta potential measurements, cryo-TEM, and fluorescence correlation spectroscopy and was found to be reversible via control of the pH. Aggregation of MSDH into closed vesicles under cytosolic conditions is at variance with the commonly held view of LD behavior, and we propose that endocytotic pathways should be considered as possible routes of LD entry into lysosomes. We further demonstrate that MSDH vesicles can be loaded with fluorophores via a solution transition from low to high pH, for subsequent release when the pH is lowered again. The ability to encapsulate molecular cargo into MSDH vesicles together with its ability to disaggregate at low pH and to permeabilize the lysosomal membrane presents an intriguing possibility to use MSDH as a delivery system.

  • 366.
    Vitiazeva, Varvara
    et al.
    Karolinska Institute, Sweden .
    Li, Jianjun
    National Research Council Canada, Canada .
    Hood, Derek W.
    MRC Harwell, England .
    Moxon, Richard E.
    University of Oxford Nuffield, England .
    Schweda, Elke
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    A novel branching pattern in the lipopolysaccharide expressed by non-typeable Haemophilus influenzae strain 12322013Inngår i: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 378, s. 114-122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report the novel branching pattern in lipopolysaccharide (LPS) expressed by non-typeable Haemophilus influenzae (NTHi) strain 1232. The strain expressed the beta-D-Glcp-(1 -andgt; 4)-[alpha-D-Galp-(1 -andgt; 4)-beta-D-Galp-(1 -andgt; 7)]-D-alpha-D-Hepp-(1 -andgt; 6)-beta-D-Glcp chain linked to the proximal heptose (HepI) of the conserved triheptosyl inner-core moiety of NTHi LPS: L-alpha-D-HepIIIp-(1 -andgt; 2)-[PEtn -andgt; 6]-L-alpha-D-HepIIp-(1 -andgt; 3)-L-alpha-D-HepIp-(1 -andgt; 5)-[PPEtn -andgt; 4]-alpha-Kdop-(2 -andgt; 6)-lipid A. The structure has been elucidated using NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and capillary electrophoresis coupled to electrospray ionization tandem mass spectrometry (CE-ESI-MSn) on O-deacylated LPS and core oligosaccharide (OS) materials, as well as HPLC-ESI-MSo on permethylated, dephosphorylated OS. It was also found that a tetrasaccharide unit bearing sialic acid [alpha-Neu5Ac-(2 -andgt; 3)-beta-D-Galp-(1 -andgt; 4)-beta-D-GlcNAcp-(1 -andgt; 3)-beta-D-Galp-(1 -andgt;] could substitute O-4 of the beta-D-Glcp linked to HepI. In addition, the distal heptose (HepIII) was substituted by PCho -andgt; 6-beta-D-Galp-(1 -andgt; at the O-2 position.

  • 367.
    Wallenhammar, Amélie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Protein modularity: Structure and interactions by NMR and SPR2016Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Protein degradation is a fundamental cornerstone of regulation of protein levels in the human body. For proper function, numerous molecular processes rely on fine-tuned communication through specific interactions between proteins. Tagging proteins by a small protein ubiquitin, called ubiquitination, is mediated by set of ubiquitin-conjugating and transferring enzymes with ubiquitin as well as substrates. This process enables specific selection of  substrate modifications, which is directly coupled to biological activity.

    In this work, the E3 ligase enzyme TRIM21, a member of the TRIM (TRIpartite Motif) protein family, and its interactions are explored. First, the three-dimensional solution structure of the TRIM21 B-box2 domain solved by nuclear magnetic resonance (NMR) spectroscopy is presented. The structure reveals how different surfaces of the B-box motif are employed for various modular interactions. Using NMR titration experiments, an exposed interaction surface is identified, described as a novel interaction patch where the B-box2 is likely to bind the RING domain. Taken together, this work establishes an extended understanding of the structural role of the B-box2 domain, and how this domain is related to flanking domains in multimodular TRIM proteins.

    Our crystal structure of TRIM21-UBE2E1 complex reveals the specific E2 recognition, which is conserved in other TRIMs. Additionally, solution scattering provides further information on the complexes and also confirms that TRIM21 RING1-91 is predominantly dimer. We also understand how the acceptor ubiquitin can be transferred to Lysine residue of TRIM211-91.

    Another highly regulated system is the RNA polymerase-II transcription, which is the first step for all protein synthesis. TATA-box Binding Protein (TBP) is an essential subunit for initiating the gene transcription, which is regulated by number of other transcription factors. Among these, the oncoprotein c-Myc regulates the transcription by directly mediating its interaction with TBP. The interplay of these interaction and competing binding of TBP and c-Myc is studied in this thesis.

    Conclusively, this thesis highlights TRIM molecular recognition and its interface with E2, and also provides the first glimpse of interaction between TBP and c-Myc.

  • 368.
    Wallenhammar, Amélie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Anandapadmanaban, Madhanagopal
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. MRC, England.
    Lemak, Alexander
    University of Toronto, Canada; University of Toronto, Canada.
    Mirabello, Claudio
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Solution NMR structure of the TRIM21 B-box2 and identification of residues involved in its interaction with the RING domain2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, artikkel-id e0181551Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein ligase implicated in innate immune signaling by acting as an autoantigen and by modifying interferon regulatory factors. Here we report the three-dimensional solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21 residues 86-130, consists of a short alpha-helical segment with an N-terminal short beta-strand and two anti-parallel beta-strands jointly found the core, and adopts a RING-like fold. This beta beta alpha beta core largely defines the overall fold of the TRIM21 B-box2 and the coordination of one Zn2+ ion stabilizes the tertiary structure of the protein. Using NMR titration experiments, we have identified an exposed interaction surface, a novel interaction patch where the B-box2 is likely to bind the N-terminal RING domain. Our structure together with comparisons with other TRIM B-box domains jointly reveal how its different surfaces are employed for various modular interactions, and provides extended understanding of how this domain relates to flanking domains in TRIM proteins.

  • 369.
    Wallgren, Jakob
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Vikingsson, Svante
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Johansson, Anders
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Dahlén, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Synthesis and identification of an important metabolite of AKB-48 with a secondary hydroxyl group on the adamantyl ring2017Inngår i: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 58, nr 15, s. 1456-1458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies on the metabolism of bioactive substances containing the adamantyl moiety have shown that hydroxylation is likely to occur at a tertiary carbon of adamantane. Herein, we report the synthesis and identification of one major metabolite of AKB-48, a new illicit psychoactive substance with a hydroxyl group at a secondary carbon of the adamantyl ring. (C) 2017 Elsevier Ltd. All rights reserved.

  • 370.
    Wallgren, Jakob
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Vikingsson, Svante
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Åstrand, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Dahlén, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Synthesis and identifications of potential metabolites as biomarkers of the synthetic cannabinoid AKB-482018Inngår i: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 74, nr 24, s. 2905-2913Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AKB-48 belongs to the family of synthetic cannabinoids. It has strong binding affinity to CBI receptor and is psychoactive. It is banned in many countries including USA, Japan, Germany, New Zealand, Singapore and China etc. But the difficulty in detecting the parent compound in urine samples highlights the importance of studies of its metabolites. Here we report the synthesis of 19 potential metabolites of AKB-48, among which, compounds 2, 9, 10, 30 and 31, together with the commercially available substance 5 were identified as metabolites of AKB-48 by comparison with one authentic human urine sample and human liver microsomal data. Compounds 10 and 30 could be of use as biomarkers in detecting AKB-48 in human urine samples. (C) 2018 Elsevier Ltd. All rights reserved.

  • 371.
    Wang, Bing
    et al.
    Univ Calif Santa Barbara, CA 93106 USA.
    Queenan, Bridget N.
    Univ Calif Santa Barbara, CA 93106 USA.
    Wang, Shu
    Chinese Acad Sci, Peoples R China.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Bazan, Guillermo C.
    Univ Calif Santa Barbara, CA 93106 USA.
    Precisely Defined Conjugated Oligoelectrolytes for Biosensing and Therapeutics2019Inngår i: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 31, nr 22, artikkel-id 1806701Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Conjugated oligoelectrolytes (COEs) are a relatively new class of synthetic organic molecules with, as of yet, untapped potential for use in organic optoelectronic devices and bioelectronic systems. COEs also offer a novel molecular approach to biosensing, bioimaging, and disease therapy. Substantial progress has been made in the past decade at the intersection of chemistry, materials science, and the biological sciences developing COEs and their polymer analogues, namely, conjugated polyelectrolytes (CPEs), into synthetic systems with biological and biomedical utility. CPEs have traditionally attracted more attention in arenas of sensing, imaging, and therapy. However, the precisely defined molecular structures and interactions of COEs offer potential key advantages over CPEs, including higher reliability and fluorescence quantum efficiency, larger diversity of subcellular targeting strategies, and improved selectivity to biomolecules. Here, the unique-and sometimes overlooked-properties of COEs are discussed and the noticeable progress in their use for biological sensing, imaging, and therapy is reviewed.

  • 372.
    Wang, Chao
    et al.
    Umeå Univ, Sweden.
    Iashchishyn, Igor A.
    Umeå Univ, Sweden; Sumy State Univ, Ukraine.
    Pansieri, Jonathan
    Umeå Univ, Sweden.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Klementieva, Oxana
    Lund Univ, Sweden.
    Kara, John
    Umea Univ, Sweden.
    Horvath, Istvan
    Umea Univ, Sweden.
    Moskalenko, Roman
    Umea Univ, Sweden; Sumy State Univ, Ukraine.
    Rofougaran, Reza
    Umea Univ, Sweden.
    Gouras, Gunnar
    Lund Univ, Sweden.
    Kovacs, Gabor G.
    Med Univ Vienna, Austria.
    Shankar, S. K.
    Natl Inst Mental Hlth and Neurosci, India.
    Morozova-Roche, Ludmilla A.
    Umea Univ, Sweden.
    S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimers Disease2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 12836Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimers disease (AD) pathology. Traumatic brain injury (TBI) is viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI and may serve as a mechanistic link between TBI and AD. By analyzing the TBI and AD human brain tissues, we demonstrated that in post-TBI tissues S100A9, produced by neurons and microglia, becomes drastically abundant compared to A beta and contributes to both precursor-plaque formation and intracellular amyloid oligomerization. Conditions implicated in TBI, such as elevated S100A9 concentration, acidification and fever, provide strong positive feedback for S100A9 nucleation-dependent amyloid formation and delay in its proteinase clearance. Consequently, both intracellular and extracellular S100A9 oligomerization correlated with TBI secondary neuronal loss. Common morphology of TBI and AD plaques indicated their similar initiation around multiple aggregation centers. Importantly, in AD and TBI we found S100A9 plaques without A beta. S100A9 and A beta plaque pathology was significantly advanced in AD cases with TBI history at earlier age, signifying TBI as a risk factor. These new findings highlight the detrimental consequences of prolonged post-TBI neuroinflammation, which can sustain S100A9-driven amyloid-neurodegenerative cascade as a specific mechanism leading to AD development.

  • 373.
    Wei, Yong
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten. Univ Hlth Network, Canada; Struct Genom Consortium, Canada.
    Resetca, Diana
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Li, Zhe
    Yokohama City Univ, Japan.
    Johansson-Åkhe, Isak
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Ahlner, Alexandra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Helander, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Wallenhammar, Amélie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Morad, Vivian
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Raught, Brian
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Kokubo, Tetsuro
    Yokohama City Univ, Japan.
    Tong, Yufeng
    Struct Genom Consortium, Canada; Univ Windsor, Canada.
    Penn, Linda Z.
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Multiple direct interactions of TBP with the MYC oncoprotein2019Inngår i: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 26, nr 11, s. 1035-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -angstrom resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1(TAND1)). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1(TAND1). Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly.

  • 374.
    Weininger, Ulrich
    et al.
    Lund University, Sweden .
    Blissing, Annica T.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Hennig, Janosch
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Ahlner, Alexandra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Liu, Zhihong
    University of Calgary, Canada .
    Vogel, Hans J.
    University of Calgary, Canada .
    Akke, Mikael
    Lund University, Sweden .
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Protein conformational exchange measured by H-1 R-1 rho relaxation dispersion of methyl groups2013Inngår i: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 57, nr 1, s. 47-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Activated dynamics plays a central role in protein function, where transitions between distinct conformations often underlie the switching between active and inactive states. The characteristic time scales of these transitions typically fall in the microsecond to millisecond range, which is amenable to investigations by NMR relaxation dispersion experiments. Processes at the faster end of this range are more challenging to study, because higher RF field strengths are required to achieve refocusing of the exchanging magnetization. Here we describe a rotating-frame relaxation dispersion experiment for H-1 spins in methyl (CHD2)-C-13 groups, which improves the characterization of fast exchange processes. The influence of H-1-H-1 rotating-frame nuclear Overhauser effects (ROE) is shown to be negligible, based on a comparison of R (1 rho) relaxation data acquired with tilt angles of 90A degrees and 35A degrees, in which the ROE is maximal and minimal, respectively, and on samples containing different H-1 densities surrounding the monitored methyl groups. The method was applied to ubiquitin and the apo form of calmodulin. We find that ubiquitin does not exhibit any H-1 relaxation dispersion of its methyl groups at 10 or 25 A degrees C. By contrast, calmodulin shows significant conformational exchange of the methionine methyl groups in its C-terminal domain, as previously demonstrated by H-1 and C-13 CPMG experiments. The present R (1 rho) experiment extends the relaxation dispersion profile towards higher refocusing frequencies, which improves the definition of the exchange correlation time, compared to previous results.

  • 375.
    Wennerstrand, Patricia
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    The Communication Guide2017Annet (Annet vitenskapelig)
    Abstract [en]

    During the doctoral studies, it is essential that communication and expectations between PhD student and supervisor are clear and realistic.

    The need of supervision changes during the PhD period. It is therefore of importance that the PhD student and the supervisor take mutual responsibility in the communication and collaboration. The purpose of the communication guide is to stimulate the dialogue on these subjects.

  • 376.
    Wennerstrand, Patricia
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Mårtensson, Lars-Göran
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Söderhäll, Stefan
    Childhood Cancer Research Unit, Department of Women and Child Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm.
    Lindqvist Appell, Malin
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Zimdahl, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Methotrexate binds to recombinant thiopurine S-methyltransferase and inhibits enzyme activity after high-dose infusions in childhood leukaemia2013Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, nr 9, s. 1641-1649Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    Important drugs in the treatment of childhood acute lymphoblastic leukaemia (ALL) are 6-mercaptopurine (6-MP) and methotrexate (MTX). Thiopurine methyltransferase (TPMT) is a polymorphic enzyme causing variability in 6-MP response and toxicity. The aim of this study was to investigate the fluctuation in TPMT enzyme activity over time and the effect of high-dose MTX infusions on TPMT enzyme activity and 6-MP metabolites in paediatric ALL patients.

    Methods

    Fifty-three children with ALL treated according to the NOPHO-ALL 2000 protocol were included in the study. TPMT enzyme activity was measured at six different times starting from diagnosis until after the end of maintenance treatment. TPMT and 6-MP metabolites were measured before the initiation of high-dose MTX (HD-MTX) infusions and at 66 h post-infusion. The interaction between MTX and TPMT was investigated in vitro using recombinant TPMT protein and a leukaemic cell line.

    Results

    Forty percent of TPMT wild-type individuals had deceptively low TPMT enzyme activity according to genotype at the time of diagnosis. TPMT activity had decreased significantly 66 h after the start of HD-MTX infusions (−9.2 %; p = 0.013). MTX bound to recombinant TPMT protein severely inhibiting TPMT enzyme activity (remaining activity 16 %).

    Conclusions

    Our results show that TPMT genotyping should be performed in children with ALL, since 40 % of the children in our study who carried the wild-type TPMT gene were at risk of initial underdosing of 6-MP in cases where only TPMT enzyme activity was determined. MTX inhibits the TPMT enzyme activity after HD-MTX infusions due to protein binding.

  • 377.
    Wickham, Abeni
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Sjölander, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Bergström, Gunnar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teknisk biologi. Linköpings universitet, Tekniska fakulteten.
    Wang, Ergang
    Chalmers, Sweden.
    Rajendran, Vijayalakshmi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hildesjö, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Skoglund, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking2015Inngår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 25, nr 27, s. 4274-4281Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.

  • 378.
    Wigenius, Jens
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Magnusson, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Björk, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Andersson, Olof
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    DNA Chips with Conjugated Polyelectrolytes in Resonance Energy Transfer Mode2010Inngår i: LANGMUIR, ISSN 0743-7463, Vol. 26, nr 5, s. 3753-3759Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We show how to use well-defined conjugated polyelectrolytes (CPEs) combined With Surface energy patterning to Fabricate DNA Chips utilizing A fluorescence signal amplification. Cholesterol-modified DNA strands in complex with it CPE are adsorbed to a surface energy pattern, formed by printing with soft elastomer stamps. Hybridization of the surface bound DNA strands with it short complementary strand from Solution is monitored using both fluorescence microscopy and imaging surface plasmon resonance. The CPEs act as antennas, enhancing resonance energy transfer to the dye-labeled DNA when complementary hybridization of the double strand occurs.

  • 379.
    Wohlfarth, Ariane
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden.
    Roman, Markus
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden.
    Andersson, Mikael
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden.
    Kugelberg, Fredrik C
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden.
    Diao, Xingxing
    Chemistry and Drug Metabolism Section, Clinical Pharmacology & TherapeuticsResearch Branch, Intramural Research Program, National Institute on DrugAbuse, National Institutes of Health, Baltimore, MD, 21224, USA.
    Carlier, Jeremy
    Chemistry and Drug Metabolism Section, Clinical Pharmacology & TherapeuticsResearch Branch, Intramural Research Program, National Institute on DrugAbuse, National Institutes of Health, Baltimore, MD, 21224, USA.
    Eriksson, Caroline
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board ofForensic Medicine, 58758 Linköping, Sweden.
    Huestis, Marilyn A
    School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
    Kronstrand, Robert
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758 Linköping, Sweden.
    25C-NBOMe and 25I-NBOMe metabolite studies in human hepatocytes, in vivo mouse and human urine with high-resolution mass spectrometry.2017Inngår i: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 9, nr 5, s. 680-698Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    25C-NBOMe and 25I-NBOMe are potent hallucinogenic drugs that recently emerged as new psychoactive substances. To date, a few metabolism studies were conducted for 25I-NBOMe, whereas 25C-NBOMe metabolism data are scarce. Therefore, we investigated the metabolic profile of these compounds in human hepatocytes, an in vivo mouse model and authentic human urine samples from forensic cases. Cryopreserved human hepatocytes were incubated for 3 h with 10 μM 25C-NBOMe and 25I-NBOMe; samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) on an Accucore C18 column with a Thermo QExactive; data analysis was performed with Compound Discoverer software (Thermo Scientific). Mice were administered 1.0 mg drug/kg body weight intraperitoneally, urine was collected for 24 h and analyzed (with or without hydrolysis) by LC-HRMS on an Acquity HSS T3 column with an Agilent 6550 QTOF; data were analyzed manually and with WebMetabase software (Molecular Discovery). Human urine samples were analyzed similarly. In vitro and in vivo results matched well. 25C-NBOMe and 25I-NBOMe were predominantly metabolized by O-demethylation, followed by O-di-demethylation and hydroxylation. All methoxy groups could be demethylated; hydroxylation preferably occurred at the NBOMe ring. Phase I metabolites were extensively conjugated in human urine with glucuronic acid and sulfate. Based on these data and a comparison with synthesized reference standards for potential metabolites, specific and abundant 25C-NBOMe urine targets are 5'-desmethyl 25C-NBOMe, 25C-NBOMe and 5-hydroxy 25C-NBOMe, and for 25I-NBOMe 2' and 5'-desmethyl 25I-NBOMe and hydroxy 25I-NBOMe. These data will help clinical and forensic laboratories to develop analytical methods and to interpret results. Copyright © 2016 John Wiley & Sons, Ltd.

  • 380.
    WOJCIK, Mareck J.
    et al.
    Faculty of Chemistry, Jagiellonian University,.
    Hermansson, Kersti
    Institute of Chemistry, University of Uppsala.
    LINDGREN, Jan
    Institute of Chemistry, University of Uppsala.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    THEORETICAL SIMULATION OF OH AND OD STRETCHING BANDS OF ISOTOPICALLY DILUTED HDO MOLECULES IN LITHIUM FORMATE SOLUTION1994Inngår i: HYDROGEN BOND NETWORKS, 1994, Vol. 435, s. 251-254Konferansepaper (Fagfellevurdert)
  • 381.
    Wolgast, Emelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Josefsson, Ann
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Lilliecreutz, Caroline
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Reis, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Drug use in pregnant women-a pilot study of the coherence between reported use of drugs and presence of drugs in plasma2018Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, nr 4, s. 535-539Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Sweden, information on drug use during pregnancy is obtained through an interview and recorded in a standardized medical record at every visit to the antenatal care clinic throughout the pregnancy. Antenatal, delivery, and neonatal records constitute the basis for the Swedish Medical Birth Register (MBR). The purpose of this exploratory study was to investigate the reliability of reported drug use by simultaneous screening for drug substances in the blood stream of the pregnant woman and thereby validate self-reported data in the MBR. Plasma samples from 200 women were obtained at gestational weeks 10-12 and 25 and screened for drugs by using ultra-high performance liquid chromatography with time of flight mass spectrometry (UHPLC-TOF-MS). The results from the analysis were then compared to medical records. At the first sampling occasion, the drugs found by screening had been reported by 86% of the women and on the second sampling, 85.5%. Missed reported information was clearly associated with drugs for occasional use. The most common drugs in plasma taken in early and mid-pregnancy were meclizine and paracetamol. Two types of continuously used drugs, selective serotonin reuptake inhibitors and propranolol, were used. All women using them reported it and the drug screening revealed a 100% coherence. This study shows good coherence between reported drug intake and the drugs found in plasma samples, which in turn positively validates the MBR.

  • 382.
    Wolrath, Helen
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borén, Hans
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hallén, Anders
    Dept. of Dermatology and Venereology, University Hospital, Uppsala, Sweden.
    Forsum, Urban
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Trimethylamine content in vaginal secretion and its relation to bacterial vaginosis2002Inngår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 110, nr 11, s. 819-824Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The presence of a fishy odor emanating from women who present with a malodorous vaginal discharge is well known. The odor is due to bacterial reduction of trimethylamine oxide to trimethylamine (TMA) in vaginal secretion. The release of TMA from specimens of vaginal fluid following the addition of alkali is often used in making a clinical diagnosis of bacterial vaginosis (BV). We now report a sensitive gas chromatographic method for analysis and quantification of TMA in vaginal fluid in which weighed samples were used. In addition, a proper diagnosis of BV was obtained using Gram-stained smears of the vaginal fluid according to the method of Nugent et al. (R. P. Nugent et al., J Clin Microbiol 1991;29:297–301). We also diagnosed BV according to Hallén et al. (A. Hallén et al. Genitourin Med 1987;63:386–9). TMA was present in all women with a Nugent score between 7 and 10 and in almost all women diagnosed with BV according to the method of Hallén et al. TMA was not found or was only found in very low concentrations in vaginal fluid from women with Nugent scores of 0 to 3. TMA was also found in four women with a negative sniff test. It seems that high levels of TMA in samples of vaginal fluid are typical for BV regardless of the scoring method used for diagnosis. However, low levels of TMA, <5 μg/g vaginal fluid, do not always correlate with BV.

  • 383.
    Wolrath, Helen
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Forsum, Urban
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Larsson, Per-Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borén, Hans
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Analysis of bacterial vaginosis-related amines in vaginal fluid by gas chromatography and mass spectrometry2001Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, nr 11, s. 4026-4031Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The presence of various amines in vaginal fluid from women with malodorous vaginal discharge has been reported before. The investigations have used several techniques to identify the amines. However, an optimized quantification, together with a sensitive analysis method in connection with a diagnostic procedure for vaginal discharge, including the syndrome of bacterial vaginosis, as defined by the accepted “gold standard,” has not been done before. We now report a sensitive gas chromatographic and mass spectrometric method for identifying the amines isobutylamine, phenethylamine, putrescine, cadaverine, and tyramine in vaginal fluid. We used weighted samples of vaginal fluid to obtain a correct quantification. In addition, a proper diagnosis was obtained using Gram-stained smears of the vaginal fluid that were Nugent scored according to the method of Nugent et al. (R. P. Nugent et al., J. Clin. Microbiol., 29:297–301, 1991). We found that putrescine, cadaverine, and tyramine occurred in high concentrations in vaginal fluid from 24 women with Nugent scores between 7 and 10. These amines either were not found or were found only in very low concentrations in vaginal fluid from women with Nugent scores of 0 to 3. There is a strong correlation between bacterial vaginosis and the presence of putrescine, cadaverine, and tyramine in high concentrations in vaginal fluid.

  • 384.
    Wu, Xiongyu
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Eriksson, Caroline
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Wohlfarth, Ariane
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Wallgren, Jakob
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Kronstrand, Robert
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Josefsson, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Dahlén, Johan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Synthesis and identification of metabolite biomarkers of 25C-NBOMe and 25I-NBOMe2017Inngår i: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 73, nr 45, s. 6393-6400Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Synthetic routes have been developed for synthesis of potential metabolites of 25C-NBOMe and 25I-NBOMe. Nine potential metabolites have been synthesized, among which compounds 8 and 20a could be used as metabolite biomarkers of 25C-NBOMe and 20b of 25I-NBOMe in urinary detection at forensic laboratories to prove intake. (C) 2017 Elsevier Ltd. All rights reserved.

  • 385.
    Wu, Xiongyu
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Silverå Ejneby, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Ottosson, Nina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Elinder, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    A Suzuki-Miyaura Coupling of ortho-Hydroxyaryl Bromide with Isopropenylboronic Pinacol Ester: Synthesis of the Potassium-Channel Opener (+)-Callitrisic Acid2018Inngår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 14, s. 1730-1734Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A Suzuki-Miyaura coupling reaction of ortho-hydroxy-aromatic bromide 8 with isopropenylboronic acid pinacol ester has been investigated. It was found that the catalyst of Pd-2(dba)(3)/PCy3 in dioxan-water gave good yield by suppressing the formation of isomeric side product 14. (+)-Callitrisic acid was synthesized from (+)-podocarpic acid using this condition with an overall yield of 54 % in about five steps. (+)-Callitrisic acid was found to be almost three times more potent than dehydroabietic acid to open a voltage-gated potassium channel.

  • 386.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Danielsson, Örjan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Finding the Optimum Chloride-Based Chemistry for Chemical Vapor Deposition of SiC2014Inngår i: ECS Journal of Solid State Science and Technology, ISSN 2162-8769, E-ISSN 2162-8777, Vol. 3, nr 10, s. P320-P323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chemical vapor deposition of silicon carbide with a chloride-based chemistry can be done using several different silicon and carbon precursors. Here, we present a comparative study of SiCl4, SiHCl3, SiH4+HCl, C3H8, C2H4 and CH4 in an attempt to find the optimal precursor combination. We find that while the chlorinated silanes SiCl4 and especially SiHCl3 give higher growth rate than natural silane and HCl, SiH4+HCl gives better morphology at C/Si around 1 and SiCl4 gives the best morphology at low C/Si. Our study shows no effect on doping incorporation with precursor chemistry. We suggest that these results can be explained by the number of reaction steps in the gas phase chemical reaction mechanisms for producing SiCl2, which is the most important Si species, and by formation of organosilicons in the gas phase. As carbon precursor, C3H8 or C2H4 are more or less equal in performance with a slight advantage for C3H8, CH4 is however not a carbon precursor that should be used unless extraordinary growth conditions are needed.

  • 387.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Gueorguiev Ivanov, Ivan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Reduction of structural defects in thick 4H-SiC epitaxial layers grown on 4° off-axis substrates2013Inngår i: Journal of Applied Physics, ISSN 0021-8979, E-ISSN 1089-7550, Vol. 113, nr 22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    By carefully controlling the surface chemistry of the chemical vapor deposition process for silicon carbide (SiC), 100 μm thick epitaxial layers with excellent morphology were grown on 4° off-axis SiC substrates at growth rates exceeding 100 μm/h. In order to reduce the formation of step bunching and structural defects, mainly triangular defects, the effect of varying parameters such as growth temperature, C/Si ratio, Cl/Si ratio, Si/H2 ratio, and in situ pre-growth surface etching time are studied. It was found that an in-situ pre growth etch at growth temperature and pressure using 0.6% HCl in hydrogen for 12 min reduced the structural defects by etching preferentially on surface damages of the substrate surface. By then applying a slightly lower growth temperature of 1575 °C, a C/Si ratio of 0.8, and a Cl/Si ratio of 5, 100 μm thick, step-bunch free epitaxial layer with a minimum triangular defect density and excellent morphology could be grown, thus enabling SiC power device structures to be grown on 4° off axis SiC substrates.

  • 388.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Kalered, Emil
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Danielsson, Örjan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Nilsson, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Ivanov, Ivan Gueorguiev
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Ojamäe, Lars
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Brominated chemistry for chemical vapor deposition of electronic grade SiC2015Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 27, nr 3, s. 793-801Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chlorinated chemical vapor deposition (CVD) chemistry for growth of homoepitaxial layers of silicon carbide (SiC) has paved the way for very thick epitaxial layers in short deposition time as well as novel crystal growth processes for SiC. Here, we explore the possibility to also use a brominated chemistry for SiC CVD by using HBr as additive to the standard SiC CVD precursors. We find that brominated chemistry leads to the same high material quality and control of material properties during deposition as chlorinated chemistry and that the growth rate is on average 10 % higher for a brominated chemistry compared to chlorinated chemistry. Brominated and chlorinated SiC CVD also show very similar gas phase chemistries in thermochemical modelling. This study thus argues that brominated chemistry is a strong alternative for SiC CVD since the deposition rate can be increased with preserved material quality. The thermochemical modelling also suggest that the currently used chemical mechanism for halogenated SiC CVD might need to be revised.

  • 389.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Effect of process parameters on dislocation density in thick 4H-SiC epitaxial layers grown by chloride-based CVD on 4 degrees off-axis substrates2014Inngår i: SILICON CARBIDE AND RELATED MATERIALS 2013, PTS 1 AND 2, Trans Tech Publications , 2014, Vol. 778-780, s. 159-162Konferansepaper (Fagfellevurdert)
    Abstract [en]

    The effect of process parameters such as growth temperature, C/Si ratio, etching time, and Si/H2 ratio on dislocation density was investigated by performing KOH etching on 100 mu m thick epitaxial layers grown on 4 degrees off axis 4H-SiC substrates at various growth conditions by a chemical vapor deposition (CVD) process using a chloride-based chemistry to achieve growth rates exceeding 100 mu m/h. We observe that the growth temperature and the growth rate have no significant influence on the dislocation density in the grown epitaxial layers. A low C/Si ratio increases the density of threading screw dislocations (TSD) markedly. The basal plane dislocation (BPD) density was reduced by using a proper in-situ etch prior to growth.

  • 390.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Sukkaew, Pitsiri
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Ivanov, Ivan Gueorguiev
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Danielsson, Örjan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    On the use of methane as a carbon precursor in Chemical Vapor Deposition of silicon carbide2014Inngår i: Journal of Crystal Growth, ISSN 0022-0248, E-ISSN 1873-5002, Vol. 390, s. 24-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is generally considered that methane is not a suitable carbon precursor for growth of silicon carbide (SiC) epitaxial layers by Chemical Vapor Deposition (CVD) since its use renders epitaxial layers with very high surface roughness. In this work we demonstrate that in fact SiC epitaxial layers with high-quality morphology can be grown using methane. It is shown that a key factor in obtaining high-quality material is tuning the C/Si ratio of the process gas mixture to a region where the growth is limited neither by carbon nor by silicon supplies. From the growth characteristics presented here, we argue that the reactivity of methane with the SiC surface is much higher than generally assumed in SiC CVD modeling today.

  • 391.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Stenberg, Pontus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Don Booker, Ian
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Gueorguiev Ivanov, Ivan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Process stability and morphology optimization of very thick 4H-SiC epitaxial layers grown by chloride-based CVD2013Inngår i: Journal of Crystal Growth, ISSN 0022-0248, E-ISSN 1873-5002, Vol. 380, s. 55-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of a chemical vapor deposition (CVD) process for very thick silicon carbide (SiC) epitaxial layers suitable for high power devices is demonstrated by epitaxial growth of 200 nm thick, low doped 4H-SiC layers with excellent morphology at growth rates exceeding 100 nm/h. The process development was done in a hot wall CVD reactor without rotation using both SiCl4 and SiH4+HCl precursor approaches to chloride based growth chemistry. A C/Si ratio andlt;1 and an optimized in-situ etch are shown to be the key parameters to achieve 200 nm thick, low doped epitaxial layers with excellent morphology.

  • 392.
    Yazdanfar, Milan
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Stenberg, Pontus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Don Booker, Ian
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Gueorguiev Ivanov, Ivan
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Pedersen, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Kordina, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Janzén, Erik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska högskolan.
    Morphology optimization of very thick 4H-SiC epitaxial layers2013Inngår i: SILICON CARBIDE AND RELATED MATERIALS 2012, Trans Tech Publications , 2013, Vol. 740-742, s. 251-254Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Epitaxial growth of about 200 gm thick, low doped 4H-SiC layers grown on n-type 8 degrees off-axis Si-face substrates at growth rates around 100 mu m/h has been done in order to realize thick epitaxial layers with excellent morphology suitable for high power devices. The study was done in a hot wall chemical vapor deposition reactor without rotation. The growth of such thick layers required favorable pre-growth conditions and in-situ etch. The growth of 190 gm thick, low doped epitaxial layers with excellent morphology was possible when the C/Si ratio was below 0.9. A low C/Si ratio and a favorable in-situ etch are shown to be the key parameters to achieve 190 gm thick epitaxial layers with excellent morphology.

  • 393.
    Young, Rosanna E. B.
    et al.
    UCL, England University of Oxford, England .
    Twelkmeyer, Brigitte
    Karolinska Institute, Sweden .
    Vitiazeva, Varvara
    Karolinska Institute, Sweden .
    Power, Peter M.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan. University of Oxford, England.
    Schweda, Elke
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hood, Derek W.
    University of Oxford, England MRC Harwell, England .
    Haemophilus parainfluenzae expresses diverse lipopolysaccharide O-antigens using ABC transporter and Wzy polymerase-dependent mechanisms2013Inngår i: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 303, nr 8, s. 603-617Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipopolysaccharide O-antigens are the basis of serotyping schemes for Gram negative bacteria and help to determine the nature of host-bacterial interactions. Haemophilus parainfluenzae is a normal commensal of humans but is also an occasional pathogen. The prevalence, diversity and biosynthesis of O-antigens were investigated in this species for the first time. 18/18 commensal H. parainfluenzae isolates contain a O-antigen biosynthesis gene cluster flanked by glnA and pepB, the same position as the hmg locus for tetrasaccharide biosynthesis in Haemophilus influenzae. The O-antigen loci show diverse restriction digest patterns but fall into two main groups: (1) those encoding enzymes for the synthesis and transfer of Fuc-NAc4N in addition to the Wzy-dependent mechanism of O-antigen synthesis and transport and (2) those encoding galactofuranose synthesis/transfer enzymes and an ABC transporter. The other glycosyltransferase genes differ between isolates. Three H. parainfluenzae isolates fell outside these groups and are predicted to synthesise O-antigens containing ribitol phosphate or deoxytalose. Isolates using the ABC transporter system encode a putative O-antigen ligase, required for the synthesis of O-antigen-containing LPS glycoforms, at a separate genomic location. The presence of an O-antigen contributes significantly to H. parainfluenzae resistance to the killing effect of human serum in vitro. The discovery of O-antigens in H. parainfluenzae is striking, as its close relative H. influenzae lacks this cell surface component.

  • 394.
    Zeglio, Erica
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Vagin, Mikhail
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Musumeci, Chiara
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Ajjan, Fátima
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Gabrielsson, Roger
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Trinh, Xuan thang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska fakulteten.
    Nguyen, Son Tien
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Halvledarmaterial. Linköpings universitet, Tekniska fakulteten.
    Maziz, Ali
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Solin, Niclas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska fakulteten.
    Conjugated Polyelectrolyte Blends for Electrochromic and Electrochemical Transistor Devices2015Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 27, nr 18, s. 6385-6393Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two self-doped conjugated polyelectrolytes, having semiconducting and metallic behaviors, respectively, have been blended from aqueous solutions in order to produce materials with enhanced optical and electrical properties. The intimate blend of two anionic conjugated polyelectrolytes combine the electrical and optical properties of these, and can be tuned by blend stoichiometry. In situ conductance measurements have been done during doping of the blends, while UV vis and EPR spectroelectrochemistry allowed the study of the nature of the involved redox species. We have constructed an accumulation/depletion mode organic electrochemical transistor whose characteristics can be tuned by balancing the stoichiometry of the active material.

  • 395.
    Zhang, Jun
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Synthesis and characterization of fluorescent stilbene-based probes targeting amyloid fibrils2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by two main protein aggregate hallmarks in the brain: extracellular deposition of the amyloid-β (Aβ) in senile plaques and intracellular neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein. The past decade has seen great progress in the development of imaging probes for the non-invasive detection of Aβ and tau aggregates. Here positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), are highly promising technologies for clinical diagnostics. However, as a research tool, optical imaging is superior because it is real-time, sensitive, inexpensive, not radioactive and that it in particular affords high-resolution studies both in vitro and in vivo. Fluorescent probes are especially useful for designing novel binding scaffolds for structure investigations of protein aggregates. This thesis describes design, synthesis and evaluation of a series of fluorescent probes for detection of amyloid fibrils, especially Aβ or tau aggregates in vitro.

    Firstly, trans-stilbenoid vinylbenzene-1,2-diol with benzene, naphthalene, anthracene, and pyrene are investigated with respect to their photophysical properties free in solution and when bound to amyloid fibrils, including time-resolved fluorescence measurements. It is noted that the extended conjugated systems retained the amyloid targeting properties of the probes and both the anthracene and pyrene moieties extensively enhanced the fluorescence intensity and prolonged lifetimes.

    Secondly, the synthesis of two molecules, Py1SA and Py2SA, based on pyrene linked to salicylic acid via a trans-stilbene C = C bond is presented. The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils as well as to fibrils from four other distinct proteins. Additionally, excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) is observed for the anionic form of the probes in polar solvents. This is likely the reason for the spectral differences of the probes when bound to amyloid fibrils.

    Moreover, the synthesis of a further development of the Congo red analogue X-34 [2,5-bis(4’-hydroxy-3’-carboxy-styryl) benzene] by rational design and synthesis is described. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of Aβ1-42 and tau as well as selectivity towards the corresponding disease-associated protein aggregates in human post mortem AD tissue.

    Lastly, the synthesis of a set of 2,1,3-benzothiadiazole (BTD)-based ligands with different conjugated spacers and variable patterns of OH substitutions of bis-styryl-BTD prototypes were developed. Aβ binding affinities (Aβ1-42 and Aβ1-40 fibrils) and the specificity towards Aβ plaques of all ligands were determined. These findings extend the structure to activity relationships of BTD-based ligands for Aβ fibril binding.

    Throughout the studies in this dissertation, new interesting properties of small molecule fluorescence probes have been discovered and analyzed. This knowledge should facilitate the development of noninvasive probes for early detection of Alzheimer's disease and to distinguish different Aβ fibril polymorphs.

    Delarbeid
    1. trans-Stilbenoids with Extended Fluorescence Lifetimes for the Characterization of Amyloid Fibrils
    Åpne denne publikasjonen i ny fane eller vindu >>trans-Stilbenoids with Extended Fluorescence Lifetimes for the Characterization of Amyloid Fibrils
    Vise andre…
    2017 (engelsk)Inngår i: ACS Omega, ISSN 2470-1343, Vol. 2, nr 8, s. 4693-4704Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    It was previously reported that two naphthyl-based trans-stilbene probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (1) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (3), can bind to both native transthyretin (TTR) and misfolded protofibrillar TTR at physiological concentrations, displaying distinct emission maxima bound to the different conformational states (>100 nm difference). To further explore this amyloid probe scaffold to obtain extended fluorescence lifetimes, two new analogues with expanded aromatic ring systems (anthracene and pyrene), (E)-4-(2-(anthracen-2-yl)vinyl)benzene-1,2-diol (4) and (E)-4-(2-(pyren-2-yl)vinyl)benzene-1,2-diol (5), were synthesized employing the palladium-catalyzed Mizoroki–Heck reaction. (E)-4-Styrylbenzene-1,2-diol (2), 3, 4, and 5 were investigated with respect to their photophysical properties in methanol and when bound to insulin, lysozyme, and Aβ1-42 fibrils, including time-resolved fluorescence measurements. In conclusion, 4 and 5 can bind to both native and fibrillar TTR, becoming highly fluorescent. Compounds 2–5 bind specifically to insulin, lysozyme, and Aβ1-42 fibrils with an apparent fluorescence intensity increase and moderate binding affinities. The average fluorescence lifetimes of the probes bound to Aβ1-42 fibrils are 1.3 ns (2), 1.5 ns (3), 5.7 ns (4), and 29.8 ns (5). In summary, the variable aromatic moieties of the para-positioned trans-stilbenoid vinyl-benzene-1,2-diol with benzene, naphthalene, anthracene, and pyrene showed that the extended conjugated systems retained the amyloid targeting properties of the probes. Furthermore, both the anthracene and pyrene moieties extensively enhanced the fluorescence intensity and prolonged lifetimes. These attractive probe properties should improve amyloid detection and characterization by fluorescence-based techniques.

    sted, utgiver, år, opplag, sider
    American Chemical Society (ACS), 2017
    Emneord
    Fluorescence; Glycoproteins; Molecular association; Molecular recognition; Optical materials; Quantum transition; Spectra
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-151658 (URN)10.1021/acsomega.7b00535 (DOI)000409924000069 ()
    Tilgjengelig fra: 2018-09-28 Laget: 2018-09-28 Sist oppdatert: 2019-11-08bibliografisk kontrollert
    2. Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.
    Åpne denne publikasjonen i ny fane eller vindu >>Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.
    Vise andre…
    2018 (engelsk)Inngår i: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 19, nr 22, s. 3001-3009Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.less thanbr /greater than (© 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.)

    sted, utgiver, år, opplag, sider
    Weinheim, Germany: Wiley-VCH Verlag, 2018
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-152767 (URN)10.1002/cphc.201800823 (DOI)000450672100006 ()30183138 (PubMedID)
    Tilgjengelig fra: 2018-11-20 Laget: 2018-11-20 Sist oppdatert: 2019-11-08
    3. Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues
    Åpne denne publikasjonen i ny fane eller vindu >>Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues
    Vise andre…
    2018 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, nr 28, s. 7210-7216Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We revisited the Congo red analogue 2,5-bis(4-hydroxy-3-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimers disease (AD) pathology comprising A beta and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of A beta 1-42 (13-300nmK(d)) and Tau (16-200nmK(d)) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant A beta 1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for A pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of A fibrils.

    sted, utgiver, år, opplag, sider
    WILEY-V C H VERLAG GMBH, 2018
    Emneord
    Alzheimers disease; amyloid ligands; dyes/pigments; fluorescence; microscopy
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-148653 (URN)10.1002/chem.201800501 (DOI)000434074800013 ()29543355 (PubMedID)
    Merknad

    Funding Agencies|China Scholarship Council; Swedish Research Council [2015-04521]; Goran Gustafsson Foundation; Swedish Alzheimer Foundation; Swedish Brain foundation; Linkoping University (LiU-Neuro); NIH/NINDS [R21 NS080576]

    Tilgjengelig fra: 2018-06-18 Laget: 2018-06-18 Sist oppdatert: 2019-11-08
  • 396.
    Zhang, Jun
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konsmo, Audun
    Norwegian Univ Sci and Technol, Norway.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Obermuller, Ulrike
    Univ Tubingen, Germany; DZNE German Ctr Neurodegenerat Dis, Germany.
    Wegenast-Braun, Bettina M.
    Univ Tubingen, Germany; DZNE German Ctr Neurodegenerat Dis, Germany.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindgren, Mikael
    Norwegian Univ Sci and Technol, Norway.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Phenolic Bis-styrylbenzo[c]-1,2,5-thiadiazoles as Probes for Fluorescence Microscopy Mapping of A beta Plaque Heterogeneity2019Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 62, nr 4, s. 2038-2048Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A fluorescent bis-styryl-benzothiadiazole (BTD) with carboxylic acid functional groups (X-34/Congo red analogue) showed lower binding affinity toward A beta 1-42 and A beta 1-40 fibrils than its neutral analogue. Hence, variable patterns of neutral OH-substituted bis-styryl-BTDs were generated. All bis-styryl-BTDs showed higher binding affinity to A beta 1-42 fibrils than to A beta 1-40 fibrils. The para-OH on the phenyl rings was beneficial for binding affinity while a meta-OH decreased the affinity. Differential staining of transgenic mouse A beta amyloid plaque cores compared to peripheral coronas using neutral compared to anionic bis-styryl ligands indicate differential recognition of amyloid polymorphs. Hyperspectral imaging of transgenic mouse A beta plaque stained with uncharged para-hydroxyl substituted bis-styryl-BTD implicated differences in binding site polarity of polymorphic amyloid plaque. Most properties of the corresponding bis-styryl-BTD were retained with a rigid alkyne linker rendering a probe insensitive to cis trans isomerization. These new BTDbased ligands are promising probes for spectral imaging of different A beta fibril polymorphs.

  • 397.
    Zhang, Jun
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konsmo, Audun
    Norwegian Univ Sci and Technol, Norway.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    LeVine, Harry III
    Univ Kentucky, KY 40536 USA.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Norwegian Univ Sci and Technol, Norway.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues2018Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, nr 28, s. 7210-7216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We revisited the Congo red analogue 2,5-bis(4-hydroxy-3-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimers disease (AD) pathology comprising A beta and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of A beta 1-42 (13-300nmK(d)) and Tau (16-200nmK(d)) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant A beta 1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for A pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of A fibrils.

  • 398.
    Zhang, Jun
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindgren, Mikael
    Department of Physics, The Norwegian University of Science and Technology, Trondheim, Norway.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    trans-Stilbenoids with Extended Fluorescence Lifetimes for the Characterization of Amyloid Fibrils2017Inngår i: ACS Omega, ISSN 2470-1343, Vol. 2, nr 8, s. 4693-4704Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It was previously reported that two naphthyl-based trans-stilbene probes, (E)-4-(2-(naphthalen-1-yl)vinyl)benzene-1,2-diol (1) and (E)-4-(2-(naphthalen-2-yl)vinyl)benzene-1,2-diol (3), can bind to both native transthyretin (TTR) and misfolded protofibrillar TTR at physiological concentrations, displaying distinct emission maxima bound to the different conformational states (>100 nm difference). To further explore this amyloid probe scaffold to obtain extended fluorescence lifetimes, two new analogues with expanded aromatic ring systems (anthracene and pyrene), (E)-4-(2-(anthracen-2-yl)vinyl)benzene-1,2-diol (4) and (E)-4-(2-(pyren-2-yl)vinyl)benzene-1,2-diol (5), were synthesized employing the palladium-catalyzed Mizoroki–Heck reaction. (E)-4-Styrylbenzene-1,2-diol (2), 3, 4, and 5 were investigated with respect to their photophysical properties in methanol and when bound to insulin, lysozyme, and Aβ1-42 fibrils, including time-resolved fluorescence measurements. In conclusion, 4 and 5 can bind to both native and fibrillar TTR, becoming highly fluorescent. Compounds 2–5 bind specifically to insulin, lysozyme, and Aβ1-42 fibrils with an apparent fluorescence intensity increase and moderate binding affinities. The average fluorescence lifetimes of the probes bound to Aβ1-42 fibrils are 1.3 ns (2), 1.5 ns (3), 5.7 ns (4), and 29.8 ns (5). In summary, the variable aromatic moieties of the para-positioned trans-stilbenoid vinyl-benzene-1,2-diol with benzene, naphthalene, anthracene, and pyrene showed that the extended conjugated systems retained the amyloid targeting properties of the probes. Furthermore, both the anthracene and pyrene moieties extensively enhanced the fluorescence intensity and prolonged lifetimes. These attractive probe properties should improve amyloid detection and characterization by fluorescence-based techniques.

  • 399.
    Zhang, Jun
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wang, Jun
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Sandberg, Alexander
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Wu, Xiongyu
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    LeVine, Harry III
    Sanders-Brown Center on Aging, University of Kentucky, KY 40536-0230, Lexington, USA..
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Durbeej, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Lindgren, Mikael
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten. Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway..
    Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.2018Inngår i: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 19, nr 22, s. 3001-3009Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.less thanbr /greater than (© 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.)

  • 400.
    Zimdahl Kahlin, Anna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Helander, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Skoglund, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Mårtensson, Lars-Göran
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindqvist Appell, Malin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden2019Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 164, s. 263-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1.1.67), and to avoid severe adverse reactions caused by incorrect dosing it is recommended that the patients TPMT status be determined before the start of thiopurine treatment. This study describes the concordance between genotyping for common TPMT alleles and phenotyping in a Swedish cohort of 12,663 patients sampled before or during thiopurine treatment. The concordance between TPMT genotype and enzyme activity was 94.5%. Compared to the genotype, the first measurement of TPMT enzyme activity was lower than expected for 4.6% of the patients. Sequencing of all coding regions of the TPMT gene in genotype/phenotype discrepant individuals led to the identification of rare and novel TPMT alleles. Fifteen individuals (0.1%) with rare or novel genotypes were identified, and three TPMT alleles (TPMT*42, *43, and *44) are characterized here for the first time. These 15 patients would not have been detected as carrying a deviating TPMT genotype if only genotyping of the most common TPMT variants had been performed. This study highlights the benefit of combining TPMT genotype and phenotype determination in routine testing. More accurate dose recommendations can be made, which might decrease the number of adverse reactions and treatment failures during thiopurine treatment.

    Fulltekst tilgjengelig fra 2020-04-18 07:47
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