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  • 1.
    Abrahamsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Lundqvist, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Quantum Chemistry.
    Wolpher, Henriette
    Johansson, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Eriksson, Lars
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Rasmussen, Torben
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Becker, Hans-Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Photochemistry and Molecular Science.
    Norrby, Per-Ola
    Åkermark, Björn
    Persson, Petter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Quantum Chemistry.
    Steric influence on the excited-state lifetimes of ruthenium complexes with bipyridyl-alkanylene-pyridyl ligands.2008In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 47, no 9, p. 3540-3548Article in journal (Refereed)
    Abstract [en]

    The structural effect on the metal-to-ligand charge transfer (MLCT) excited-state lifetime has been investigated in bis-tridentate Ru(II)-polypyridyl complexes based on the terpyridine-like ligands [6-(2,2'-bipyridyl)](2-pyridyl)methane (1) and 2-[6-(2,2'-bipyridyl)]-2-(2-pyridyl)propane (2). A homoleptic ([Ru(2)(2)](2+)) and a heteroleptic complex ([Ru(ttpy)(2)](2+)) based on the new ligand 2 have been prepared and their photophysical and structural properties studied experimentally and theoretically and compared to the results for the previously reported [Ru(1)(2)](2+). The excited-state lifetime of the homoleptic Ru-II complex with the isopropylene-bridged ligand 2 was found to be 50 times shorter than that of the corresponding homoleptic Ru-II complex of ligand 1, containing a methylene bridge. A comparison of the ground-state geometries of the two homoleptic complexes shows that steric interactions involving the isopropylene bridges make the coordination to the central Ru-II ion less octahedral in [Ru(2)(2)](2+) than in [Ru(1)(2))(2+). Calculations indicate that the structural differences in these complexes influence their ligand field splittings as well as the relative stabilities of the triplet metal-to-ligand charge transfer ((MLCT)-M-3) and metal-centered ((MC)-M-3) excited states. The large difference in measured excited-state lifetimes for the two homoleptic Ru-II complexes is attributed to a strong influence of steric interactions on the ligand field strength, which in turn affects the activation barriers for thermal conversion from (MLCT)-M-3 states to short-lived (MC)-M-3 states.

  • 2.
    Abrahamsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Accelerator mass spectrometry group. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Wolpher, Henriette
    Johansson, Olof
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Kritikos, Mikael
    Eriksson, Lars
    Norrby, Per-Ola
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Sun, Licheng
    Åkermark, Björn
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    A New Strategy for the Improvement of Photophysical Properties in Ruthenium(II) Polypyridyl Complexes: Synthesis and Photophysical and Electrochemical Characterization of Six Mononuclear Ruthenium(II) Bisterpyridine-Type Complexes2005In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 44, no 9, p. 3215-3225Article in journal (Refereed)
  • 3.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Musunuri, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Proteomic Differences Between Focal And Diffuse Traumatic Brain Injury In Human Brain Tissue2018In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, no 16, p. A238-A239Article in journal (Other academic)
  • 4.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Musunuri, Sravani
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 6807Article in journal (Refereed)
    Abstract [en]

    The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.

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  • 5.
    Addinsall, Alex B.
    et al.
    Department of Physiology and PharmacologyKarolinska InstituteStockholm.
    Cacciani, Nicola
    Department of Physiology and PharmacologyKarolinska InstituteStockholm;Department of Clinical NeuroscienceKarolinska InstituteStockholm.
    Akkad, Hasem
    Department of Physiology and PharmacologyKarolinska InstituteStockholm.
    Moruzzi, Noah
    Department of Molecular Medicine and SurgeryKarolinska InstituteStockholm.
    Maestri, Alice
    Department of MedicineKarolinska InstituteStockholm.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ruas, Jorge
    Department of Physiology and PharmacologyKarolinska InstituteStockholm.
    Larsson, Lars
    Department of Physiology and PharmacologyKarolinska InstituteStockholm;Viron Molecular Medicine InstituteBostonMA.
    Ruxolitinib Prevents Ventilator Induced Diaphragm Dysfunction2022In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 36, no S1Article in journal (Refereed)
    Abstract [en]

    Mechanical ventilation (MV), however brief results in the loss of diaphragm muscle mass and strength, termed ventilator induced diaphragm dysfunction (VIDD). VIDD increases dependence, complicates and prolongs weaning and significantly increases discharge mortality rate and health care costs worldwide. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway was recently identified as an important signalling pathway implicated in VIDD, upregulated in the diaphragm following MV and limb muslces during critical care. Regulation of STAT3 is imperritve to skeletal muscle mass and function, as STAT3 is required in proper muscle growth and regeneration, while chronic activation of STAT3 is implicated in muscle dysfunction. As JAK/STAT pathway inhibition can restrict the development of chronic muscle wasting conditons, this study aimed to explore the therapeutic potential of Ruxolitinib, an approved JAK1/2 inhibitor for myelofibrosis, for treatment of CIM. We hypothesised Ruxolitinib would reduce loss of muscle mass and function associated with VIDD. Here, rats were subjected to five days controlled MV (CMV) with and without daily Ruxolitinib gavage. Five-days CMV significantly reduced diaphragm muscle size and impaired specific force, which was associated with 2-fold upregulation of P-STAT3, disrupted mitochondrial structure and respiratory function. Expression of the motor protein myosin was not affected, however CMV may alter myosin function through deamidation post translational modification. Ruxolitinib increases five-day survival rate, restored P-STAT3 expression and preserved diaphragm muscle size and specific force. These functional improvements were associated with improved mitochondrial structure, augmented mitochondrial respiratory function and reversal or augmentation of myosin deamidations. These results provide evidence of the preclinical potential of repurposing Ruxolitinib for the treatment of VIDD.

  • 6.
    Addinsall, Alex B.
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden..
    Cacciani, Nicola
    Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden.;Karolinska Inst, Dept Clin Neurosci, Solna, Sweden..
    Backeus, Anders
    Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden..
    Hedstrom, Yvette
    Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden..
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Lars
    Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden.;Karolinska Inst, Dept Clin Neurosci, Solna, Sweden.;Viron Mol Med Inst Boston, Boston, MA USA..
    Electrical stimulated GLUT4 signalling attenuates critical illness-associated muscle wasting2022In: Journal of Cachexia, Sarcopenia and Muscle, ISSN 2190-5991, E-ISSN 2190-6009, Vol. 13, no 4, p. 2162-2174Article in journal (Refereed)
    Abstract [en]

    Background Critical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a by-product of critical care, attributed to impaired recovery, long-term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood; however, loss of mechanical stimuli contributes to critical illness-associated muscle atrophy and weakness. Passive mechanical loading and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care. Methods Rats were subjected to 8 days of critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM. Results Following 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, myosin : actin ratio, and single muscle fibre maximum force normalized to cross-sectional area (CSA; specific force) were reduced by 40-50% (P < 0.0001). ES significantly reduced the loss of soleus muscle fibre CSA and myosin : actin ratio by approximately 30% (P < 0.05) yet failed to effect specific force. RNAseq pathway analysis revealed downregulation of insulin signalling in the soleus muscle following critical care, and GLUT4 trafficking was reduced by 55% leading to an 85% reduction of muscle glycogen content (P < 0.01). ES promoted phosphofructokinase and insulin signalling pathways to control levels (P < 0.05), consistent with the maintenance of GLUT4 translocation and glycogen levels. AMPK, but not AKT, signalling pathway was stimulated following ES, where the downstream target TBC1D4 increased 3 logFC (P = 0.029) and AMPK-specific P-TBC1D4 levels were increased approximately two-fold (P = 0.06). Reduction of muscle protein degradation rather than increased synthesis promoted soleus CSA, as ES reduced E3 ubiquitin proteins, Atrogin-1 (P = 0.006) and MuRF1 (P = 0.08) by approximately 50%, downstream of AMPK-FoxO3. Conclusions ES maintained GLUT4 translocation through increased AMPK-TBC1D4 signalling leading to improved muscle glucose homeostasis. Soleus CSA and myosin content was promoted through reduced protein degradation via AMPK-FoxO3 E3 ligases, Atrogin-1 and MuRF1. These results demonstrate chronic supramaximal ES reduces critical care associated muscle wasting, preserved glucose signalling, and reduced muscle protein degradation in CIM.

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  • 7.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kullinger, Merit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Plasma levels of arginines at term pregnancy in relation to mode of onset of labor and mode of childbirth2023In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 90, no 3, article id e13767Article in journal (Refereed)
    Abstract [en]

    PROBLEM: The exact biochemical mechanisms that initiate labor are not yet fully understood. Nitric oxide is a potent relaxant of uterine smooth muscles until labor starts, and its precursor is L-arginine. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines, are potent NO-inhibitors. However, arginines (dimethylarginines and L-arginine) are scarcely studied in relation to labor and childbirth. We aimed to investigate arginines in women with spontaneous (SLVB) and induced (ILVB) term labor with vaginal birth and in women undergoing elective caesarean section (ECS).

    METHOD OF STUDY: Women at gestational week 16-18 were recruited to the population-based prospective cohort study BASIC at the Uppsala University Hospital, Sweden. Plasma samples taken at start of labor were analyzed for arginines, from SLVB (n = 45), ILVB (n = 45), and ECS (n = 45), using Ultra-High Performance Liquid Chromatography. Between-group differences were assessed using Kruskal-Wallis and Mann-Whitney U-test.

    RESULTS: Women with SLVB and ILVB had higher levels of ADMA (p < .0001), SDMA (p < .05) and lower L-arginines (p < .01), L-arginine/ADMA (p < .0001), and L-arginine/SDMA (p < .01, respectively <.001) compared to ECS. However, ILVB had higher ADMA (p < .0001) and lower L-arginine (p < .01), L-arginine/ADMA (p < .0001), and L-arginine/SDMA (p < .01) compared to SLVB. Results are adjusted for gestational length at birth and cervical dilatation at sampling.

    CONCLUSION: Our novel findings of higher levels of dimethylarginines in term vaginal births compared to ECS give insights into the biochemical mechanisms of labor. These findings might also serve as a basis for further studies of arginines in complicated pregnancies and labor.

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  • 8.
    Allard, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Bäckström, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Danielsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Sjöberg, Per J.R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Comparing capillary electrophoresis: mass spectrometry fingerprints of urine samples obtained after intake of coffee, tea, or water.2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 23, p. 8946-8955Article in journal (Refereed)
    Abstract [en]

    Metabolomic fingerprinting is a growing strategy for characterizing complex biological samples without detailed prior knowledge about the metabolic system. A two-way analysis system with liquid separation and mass spectrometric detection provides detail-rich data suitable for such fingerprints. As a model study, human urine samples, obtained after intake of coffee, tea, or water, were analyzed with capillary electrophoresis electrospray ionization time-of-flight mass spectrometry (CE−ESI-TOF-MS). In-house-developed software (in Matlab) was utilized to manage and explore the large amount of data acquired (230 CE−MS runs, each with 50−100 million nonzero data points). After baseline and noise reduction, followed by suitable binning in time and m/z, the data sets comprised 9 and 14 million data points in negative and positive ESI mode, respectively. Finally, a signal threshold was applied, further reducing the number to about 100 000 data points per data set. A set of interactive exploratory tools, utilizing principal component analysis (PCA) and analysis of variance (ANOVA) results based on a general linear model, facilitated visual interpretation with score plots (for group assessment) and differential fingerprints (for “hot spot” detection). In the model study highly significant differences due to beverage intake were obtained among the 10 first principal components (p < 10−6 for two of the components in both ESI modes). Especially, the contrasts between “coffee” and “tea or water” indicated several “hot spots” with highly elevated intensities (e.g., for uncharged masses 93, 94, 109, 119, 123, 132, 148, 169, 178, 187, 190, and 193) suitable for further analysis, for example, with tandem MS.

  • 9.
    Al-Mahdi Al-Karagholi, Mohammad
    et al.
    Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark.
    Møller Hansen, Jakob
    Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark; Rigshosp Glostrup, Danish Knowledge Ctr Headache Disorders, Glostrup, Denmark.
    Abou-Kassem, Dalia
    Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark.
    Koldbro Hansted, Anna
    Univ Copenhagen, Rigshosp Glostrup, Fac Hlth & Med Sci, Glostrup Res Inst,Danish Headache Ctr, Glostrup, Denmark.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Vécsei, László
    Univ Szeged, Dept Neurol, Szeged, Hungary; Univ Szeged, MTA SZTE Neurosci Res Grp, Szeged, Hungary.
    Jansen-Olesen, Inger
    Univ Copenhagen, Rigshosp Glostrup, Fac Hlth & Med Sci, Glostrup Res Inst, Danish Headache Ctr, Glostrup, Denmark.
    Ashina, Messoud
    Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark; Rigshosp Glostrup, Danish Knowledge Ctr Headache Disorders, Glostrup, Denmark.
    Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers2021In: Pharmacology Research & Perspectives, E-ISSN 2052-1707, Vol. 9, no 2, article id e00741Article in journal (Refereed)
    Abstract [en]

    The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.

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  • 10.
    Almokhtar, Mokhtar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Wikvall, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Norlin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.2016In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 158, p. 178-188Article in journal (Refereed)
    Abstract [en]

    Vitamin D-3 is a pro-hormone, which is sequentially activated by 25- and 1 alpha-hydroxylation to form 25-hydroxyvitamin D-3 [25(OH)D-3] and 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)2D(3)], respectively. Subsequent inactivation is performed by 24-hydroxylation. These reactions are carried out by a series of CYP450 enzymes. The 25-hydroxylation involves mainly CYP2R1 and CYP27A1, whereas 1 alpha-hydroxylation and 24-hydroxylation are catalyzed by CYP27B1 and CYP24A1, respectively, and are tightly regulated to maintain adequate levels of the active vitamin D hormone, 1 alpha,25(OH)(2)D-3. Altered circulating vitamin D levels, in particular 25(OH)D-3, have been linked to several disorders of the nervous system, e.g., schizophrenia and Parkinson disease. However, little is known about the mechanisms of vitamin D actions in the neurons. In this study, we examined vitamin D metabolism and its regulation in a murine motor neuron-like hybrid cell line, NSC-34. We found that these cells express mRNAs for the four major CYP450 enzymes involved in vitamin D activation and inactivation, and vitamin D receptor (VDR) that mediates vitamin D actions. We also found high levels of CYP24A1-dependent 24,25-dihydroxyvitamin D-3 [24,25(OH)(2)D-3] production, that was inhibited by the well-known CYP enzyme inhibitor ketoconazole and by several inhibitors that are more specific for CYP24A1. Furthermore, CYP24A1 mRNA levels in NSC-34 cells were up-regulated by 1 alpha,25(OH)(2)D-3 and its synthetic analogs, EB1089 and tacalcitol. Our results suggest that NSC-34 cells could be a novel model for the studies of neuronal vitamin D metabolism and its mechanism of actions.

  • 11. Amelina, Hanna
    et al.
    Sjödin, Marcus O.D.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Cristobal, Susana
    Quantitative subproteomic analysis of age-related changes in mouse liver peroxisomes by iTRAQ LC-MS/MS2011In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 879, no 30, p. 3393-3400Article in journal (Refereed)
    Abstract [en]

    Aging is a complex multifactorial phenomenon, which is believed to result from the accumulation of cellular damage to biological macromolecules. Peroxisomes recently emerged as another important source of reactive oxygen species (ROS) production in addition to mitochondria. However, the role of these organelles in the process of aging is still not clear. The aim of this study was to characterize the changes in protein expression profiles of young (10 weeks old) versus old (18 months old) mouse liver peroxisome-enriched fractions. We have applied shotgun proteomic approach based on liquid chromatography and tandem mass spectrometry (LC-MS/MS) combined with iTRAQ (isobaric tags for relative and absolute quantitation) labeling that allows comparative quantitative multiplex analysis. Our analysis led to identification and quantification of 150 proteins, 8 out of which were differentially expressed between two age groups at a statistically significant level (p < 0.05), with folds ranging from 1.2 to 4.1. These proteins involved in peroxisornal beta-oxidation, detoxification of xenobiotics and production of ROS. Noteworthy, differences in liver proteome have been observed between as well as within different age groups. In conclusion, our subproteomic quantitative study suggests that mouse liver proteome is sufficiently maintained until certain age.

  • 12.
    Amirkhani, A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Heldin, E.
    Markides, K.E.
    Bergquist, J.
    Quantitation of tryptophan, kynurenine and kynurenic acid in human plasma by capillary liquid chromatography - electrospray ionization tandem mass spectrometry2002In: J. of Chromatography B, no 780, p. 381-387Article in journal (Refereed)
  • 13.
    Amirkhani, Ardeshir
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Heldin, Eva
    Markides, Karin E.
    Bergquist, Jonas
    Quantitation of tryptophan, kynurenine and kynurenic acid in human plasma by capillary liquid chromatography - electrospray2002In: Journal of Chromatography B, Vol. 780, no 2, p. 381-387Article in journal (Refereed)
  • 14.
    Amirkhani, Ardeshir
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Rajda, Cecilia
    Arvidsson, Björn
    Bencsik, Krisztina
    Boda, Krisztina
    Seres, Erika
    Markides, Karin E.
    Vecsei, Laszlo
    Bergquist, Jonas
    Beta-interferon effects the tryptophan metabolism in the plasma of multiple sclerosis patientsManuscript (Other academic)
  • 15.
    Amirkhani, Ardeshir
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Rajda, Cecilia
    Arvidsson, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bencsik, Krisztina
    Boda, Krisztina
    Seres, Erika
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Vecsei, Laszlo
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients2005In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 12, no 8, p. 625-631Article in journal (Refereed)
    Abstract [en]

    Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.

  • 16.
    Amirkhani, Ardeshir
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Wetterhall, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Nilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Danielsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
    Comparison between different sheathless electrospray emitter configurations regarding the performance of nanoscale liquid chromatography time-of-flight mass spectrometry analysis2004In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1033, no 2, p. 257-266Article in journal (Refereed)
    Abstract [en]

    Four different sheathless electrospray ionization (ESI) configurations were investigated for a nano liquid chromatography (LC) system. The studied configurations were: a column with an integrated emitter, with the ESI potential applied before or after the column, and a column with separate emitter, with the ESI voltage applied at a union before the emitter or at the emitter tip. The results indicates that the efficiency of the LC system is rather independent of the configuration when using 95 μm i.d. columns, acetic mobile phase and standard peptides as a sample. Introduction of post column dead volume seems not to be a critical issue at least with flow rates down to 600 nl/min.

  • 17.
    Amortegui, Julio Cesar Espana
    et al.
    Swedish Food Agcy, Sci Dept, Box 622, SE-75126 Uppsala, Sweden.;Univ Nacl Colombia, Sci Fac, Chem Dept, Cr 45 N 26-85,POB 111321, Bogota, Colombia..
    Pekar, Heidi
    Swedish Food Agcy, Sci Dept, Box 622, SE-75126 Uppsala, Sweden.;Stockholm Water & Waste Co, Bryggerivagen 10, SE-10636 Stockholm, Sweden..
    Retrato, Mark Dennis Chico
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Persson, Malin
    Swedish Food Agcy, Sci Dept, Box 622, SE-75126 Uppsala, Sweden..
    Karlson, Bengt
    Swedish Meteorol & Hydrol Inst, Res & Dev, Oceanog, Sven Kallfelts Gata 15, SE-42671 Vastra Frolunda, Sweden..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zuberovic, Aida
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Swedish Food Agcy, Sci Dept, Box 622, SE-75126 Uppsala, Sweden..
    LC-MS/MS Analysis of Cyanotoxins in Bivalve Mollusks: Method Development, Validation and First Evidence of Occurrence of Nodularin in Mussels (Mytilus edulis) and Oysters (Magallana gigas) from the West Coast of Sweden2023In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 15, no 5, article id 329Article in journal (Refereed)
    Abstract [en]

    In this paper, an LC-MS/MS method for the simultaneous identification and quantification of cyanotoxins with hydrophilic and lipophilic properties in edible bivalves is presented. The method includes 17 cyanotoxins comprising 13 microcystins (MCs), nodularin (NOD), anatoxin-a (ATX-a), homoanatoxin (h-ATX) and cylindrospermopsin (CYN). A benefit to the presented method is the possibility for the MS detection of MC-LR-[Dha7] and MC-LR-[Asp3] as separately identified and MS-resolved MRM signals, two congeners which were earlier detected together. The performance of the method was evaluated by in-house validation using spiked mussel samples in the quantification range of 3.12-200 mu g/kg. The method was found to be linear over the full calibration range for all included cyanotoxins except CYN for which a quadratic regression was used. The method showed limitations for MC-LF (R-2 = 0.94), MC-LA (R-2 <= 0.98) and MC-LW (R-2 <= 0.98). The recoveries for ATX-a, h-ATX, CYN, NOD, MC-LF and MC-LW were lower than desired (<70%), but stable. Despite the given limitations, the validation results showed that the method was specific and robust for the investigated parameters. The results demonstrate the suitability of the method to be applied as a reliable monitoring tool for the presented group of cyanotoxins, as well as highlight the compromises that need to be included if multi-toxin methods are to be used for the analysis of cyanotoxins with a broader range of chemical properties. Furthermore, the method was used to analyze 13 samples of mussels (Mytilus edulis) and oysters (Magallana gigas) collected in the 2020-2022 summers along the coast of Bohuslan (Sweden). A complementary qualitative analysis for the presence of cyanotoxins in phytoplankton samples collected from marine waters around southern Sweden was performed with the method. Nodularin was identified in all samples and quantified in bivalve samples in the range of 7-397 <= g/kg. Toxins produced by cyanobacteria are not included in the European Union regulatory monitoring of bivalves; thus, the results presented in this study can be useful in providing the basis for future work including cyanotoxins within the frame of regulatory monitoring to increase seafood safety.

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  • 18.
    Andersson, Christoffer R.
    et al.
    Orebro Univ, Dept Neurol, Fac Med & Hlth, Orebro, Sweden..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Theodorsson, Elvar
    Linkoping Univ, Dept Clin Chem, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Strom, Jakob O.
    Orebro Univ, Dept Neurol, Fac Med & Hlth, Orebro, Sweden.;Linkoping Univ, Dept Clin Chem, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed)
    Abstract [en]

    Introduction: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. Aim of study: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec). Methods: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits. Results: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values >.77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained. Conclusions: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

  • 19.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Dahllöf, Tell Åke
    Droger och desperation i skilda världar: missbruk av katinon och metkatinon hotar hälsa och social utveckling.2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 20, p. 1358-1361Article, review/survey (Other academic)
    Abstract [sv]

    De betydande sociala och medicinska riskerna vid missbruk av katinon (tuggning av kat) och metkatinon (intravenös injektion av illegala synteser) har i stort sett inte uppmärksammats i svensk narkotikadebatt.

    Tullens beslag av kat visar hur det traditionella bruket importeras med immigration från framför allt Östafrika.

    Syntesrecept på metkatinon, som kan hämtas från Internet, ger produkter som orsakat manganförgiftning med svåra, irreversibla motoriska handikapp hos hundratals unga framför allt i Baltikum, Ryssland, Ukraina och Georgien. Denna »epidemi« fortgår.

    Kunskap om förekomst, kliniska symtom och spridningsrisker vid dessa missbruksformer är angelägen såväl ur ett nationellt som ett internationellt biståndsperspektiv.

  • 20.
    Artemenko, Konstantin A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Lind, Sara Bergström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Elfineh, Lioudmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mayrhofer, Corina
    Zubarev, Roman A.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Optimization of immunoaffinity enrichment and detection: toward a comprehensive characterization of the phosphotyrosine proteome of K562 cells by liquid chromatography-mass spectrometry2011In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 136, no 9, p. 1971-1978Article in journal (Refereed)
    Abstract [en]

    Phosphorylation of protein tyrosine residues regulates many cell functions and has also been proved to be involved in oncogenesis. Thus, the identification of the phosphotyrosine (pTyr) proteome of cells is a very important task. Since tyrosine phosphorylation represents only around 1% of the total human phosphoproteome, the study of pTyr proteins is rather challenging. Here we report the optimization study of the phosphotyrosine proteome using K562 cells as a model system. A substantial segment of the phosphotyrosine proteome of K562 cells was characterized by immunoaffinity enrichment with 4G10 and PYKD1 antibodies followed by LC-MS/MS analysis. 480 non-redundant pTyr peptides corresponding to 342 pTyr proteins were found. 141 pTyr peptides were not described elsewhere. The mass spectrometry approach involving high-resolving FTMS analysis of precursor ions and subsequent detection of CID fragments in a linear ion trap was considered as optimal. For detection of low abundant pTyr peptides pooling of individual immunoaffinity enrichments for one LC-MS/MS analysis was crucial. The enrichment properties of the monoclonal PYKD1 antibody were presented for the first time, also in comparison to the 4G10 antibody. PYKD1 was found to be more effective for protein enrichment (1.2 and 5% efficiency at peptide and protein level correspondingly), while 4G10 showed better results when peptide enrichment was performed (15% efficiency versus 3.6% at protein level). Substantially different subsets of the phosphoproteome were enriched by these antibodies. This finding together with previous studies demonstrates that comprehensive pTyr proteome characterization by immunoprecipitation requires multiple antibodies to be used for the affinity enrichment.

  • 21.
    Artemenko, Konstantin A
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mass-spectrometry-based characterization of oxidations in proteins2015In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 49, no 5, p. 477-93Article, review/survey (Refereed)
    Abstract [en]

    Protein modifications such as oxidations have a strong impact on protein function and activity in various organisms. High-resolution mass spectrometric techniques in combination with various sample preparation methodologies allow for the in-detail characterization of protein structures and strongly contribute to a greater understanding of the impact of protein modifications in nature. This paper outlines the general workflows for the characterization of oxidation sites in proteins by mass spectrometry (MS). Different types of oxidations are taken into consideration; both qualitative and quantitative aspects of MS-based approaches are presented with respect to oxidized proteins. Both bottom-up and top-down MS approaches are described and evaluated; a wide range of the particular applications corresponding to these techniques is also presented. Furthermore, the common advantages and downsides of these techniques are assessed. The approaches for enrichment of low-abundance oxidized proteins are extensively presented for different cysteine oxidations and protein carbonylations. A short description about databases and bioinformatic software solutions for oxidative protein prediction, identification, and biological interpretation is also given in this review.

  • 22.
    Artemenko, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Horakova, Jana
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Steinberger, Birgit
    Besenfelder, Urban
    Brem, Gottfried
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mayrhofer, Corina
    A proteomic approach to monitor the dynamic response of the female oviductal epithelial cell surface to male gametes2015In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 113, p. 1-14Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Sophisticated strategies to analyze cell surface proteins are indispensable to study fundamental biological processes, such as the response of cells to environmental changes or cell-cell communication. Herein, we describe a refined mass spectrometry-based approach for the specific characterization and quantitation of cell surface proteins expressed in the female reproductive tract. The strategy is based on in situ biotinylation of rabbit oviducts, affinity enrichment of surface exposed biotin tagged proteins and dimethyl labeling of the obtained tryptic peptides followed by LC-MS/MS analysis. This approach proved to be sensitive enough to analyze small sample amounts (<1mug) and allowed further to trace the dynamic composition of the surface proteome of the oviductal epithelium in response to male gametes. The relative protein expression ratios of 175 proteins were quantified. Thirty-one of them were found to be altered over time, namely immediately, 1h and 2h after insemination compared to the time-matched control groups. Functional analysis demonstrated that structural reorganization of the oviductal epithelial cell surface was involved in the early response of the female organ to semen. In summary, this study outlines a workflow that is capable to monitor alterations in the female oviduct that are related to key reproductive processes in vivo. BIOLOGICAL SIGNIFICANCE: The proper interaction between the female reproductive tract, in particular, the oviduct and the male gametes, is fundamental to fertilization and embryonic development under physiological conditions. Thereby the oviductal epithelial cell surface proteins play an important role. Besides their direct interaction with male gametes, these molecules participate in signal transduction and, thus, are involved in the mandatory cellular response of the oviductal epithelium. In this study we present a refined LC-MS/MS based workflow that is capable to quantitatively analyze the expression of oviductal epithelial cell surface proteins in response to insemination in vivo. A special focus was on the very early interaction between the female organ and the male gametes. At first, this study clearly revealed an immediate response of the surface proteome to semen, which was modulated over time. The described methodology can be applied for studies of further distinct biological events in the oviduct and therefore contribute to a deeper insight into the formation of new life.

  • 23.
    Arvidsson, Björn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Allard, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Sjöberg, Per Johan Ragnar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.2009In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 3, p. 291-297Article in journal (Refereed)
    Abstract [en]

    This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.

  • 24.
    Arvidsson, Björn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Johannesson, Nina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Citterio, Attilio
    Righetti, Pier Giorgio
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    High throughput analysis of tryptophan metabolites in a complex matrix using capillary electrophoresis coupled to time-of-flight mass spectrometry2007In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1159, no 1-2, p. 154-158Article in journal (Refereed)
    Abstract [en]

    A capillary electrophoresis method for separation and detection with time-of-flight mass spectrometry is described for tryptophan metabolites in the kynurenic pathway. Tryptophan metabolites are usually difficult to detect with electrospray mass spectrometry since they have low surface activity and occur in low nanomolar to micromolar range in body fluids. Modification of the silica-wall with 1-(4-iodobutyl)4-aza-1-azoniabicyclo[2,2,2]octane iodide, also named M7C4I, has successfully been used to deactivate the fused silica wall and generate a stable reversed electroosmotic flow. Utilizing this advantage together with electrospray ionization time-of-flight mass spectrometry, which generates high resolution and fast acquisition monitoring of species, proved to be successful even for such a complex matrix like human cerebrospinal fluid.

  • 25.
    Asser, Andres
    et al.
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Koks, Sulev
    Univ Tartu, Dept Pathophysiol, Tartu, Estonia..
    Snellman, Anniina
    Univ Turku, Turku PET Ctr, Turku, Finland..
    Haaparanta-Solin, Merja
    Univ Turku, Turku PET Ctr, Turku, Finland..
    Arponen, Eveliina
    Univ Turku, Turku PET Ctr, Turku, Finland..
    Gronroos, Tove
    Univ Turku, Turku PET Ctr, Turku, Finland..
    Nairismagi, Jaak
    Tallinn Univ Technol, Inst Gene Technol, Tallinn, Estonia..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Soomets, Ursel
    Univ Tartu, Dept Biochem, Tartu, Estonia..
    Piip, Piret
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Eltermaa, Mall
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Sauk, Martin
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Lindmae, Hanna
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Rinne, Juha O.
    Univ Turku, Turku PET Ctr, Turku, Finland.;Turku Univ Hosp, Dept Neurol, Turku, Finland..
    Taba, Pille
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-50409 Tartu, Estonia..
    Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese2016In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1652, p. 97-102Article in journal (Refereed)
    Abstract [en]

    Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [C-11]dihydrotetrabenazine ([C-11]DTBZ). After 27 weeks of treatment [C-11]DTBZ autoradiography demonstrated a significant increase in the striatum to -cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [C-11]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate.

  • 26.
    Asser, Andres
    et al.
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-51014 Tartu, Estonia.
    Koks, Sulev
    Univ Western Australia, Perron Inst Neurol & Translat Sci, Perth, WA, Australia.
    Soomets, Ursel
    Univ Tartu, Dept Biochem, Ravila 19, EE-50411 Tartu, Estonia.
    Terasmaa, Anton
    Univ Tartu, Dept Physiol, Ravila 19, EE-50411 Tartu, Estonia.
    Sauk, Martin
    Univ Tartu, Inst Mol & Cell Biol, Riia 23, EE-51010 Tartu, Estonia.
    Eltermaa, Mall
    Univ Tartu, Inst Biomed & Translat Med, Ravila 19, EE-50411 Tartu, Estonia.
    Piip, Piret
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-51014 Tartu, Estonia.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Taba, Pille
    Univ Tartu, Dept Neurol & Neurosurg, Puusepa 8, EE-51014 Tartu, Estonia.
    Acute effects of methcathinone and manganese in mice: A dose response study2019In: Heliyon, E-ISSN 2405-8440, Vol. 5, no 9, article id e02475Article in journal (Refereed)
    Abstract [en]

    An intravenously injectable illicit drug made by mixing pseudoephedrine, potassium permanganate, vinegar and water, yielding methcathinone (Mcat) and manganese (Mn), induces an extrapyramidal syndrome with parkinsonism, dystonia, gait and balance disorders similar to manganism. Although the cause of the syndrome is largely attributed to Mn, the interaction of the drug's individual components is not known and the role of Mcat is possibly underestimated. Aim of the present study was to analyze dose-dependent behavioral effects of the mixture and its two main active components Mcat and Mn in an acute setting and determine the lethal doses of each substance. Three groups of C57BL/6 mice were injected intraperitoneally with (1) the drug mixture containing 10, 25, 50, 100 or 150 mg of Mcat and respectively 1.6, 3.8, 6.9, 17.1 and 22.6 mg of Mn per kilogram of body weight; (2) 10, 25, 50, 100, 150, 200 or 300 mg of racemic Mcat/kg of body weight; (3) MnCl2 10, 25 or 50 mg/kg of body weight. Locomotor activity of the animals, various signs and time of death were recorded. Lower doses (10 and 25 mg/kg) of Mcat had a clear motor activity stimulating effect and this was clearly dose-dependent. High doses of Mcat produced epileptic seizures in 74% of the animals and became lethal with the highest doses. Similarly, the mixture had a clear dose-dependent stimulating effect and the higher doses became lethal. The LD50 of the pseudoephedrine mixture was 110.2 mg of Mcat/kg and for pure Mcat 201.7 mg/kg. Mn did not prove to be lethal in doses up to 50 mg/kg, but had a strong dose dependent inhibitory effect on the animals' behavior. Our data reveal that both Mn and Mcat have a significant role in the toxicity of the mixture.

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  • 27.
    Attermeyer, Katrin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. WasserCluster Lunz, Lunz Am See, Austria.
    Catalan, Nuria
    Catalan Inst Water Res ICRA, Girona, Spain.
    Einarsdóttir, Karólina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Freixa, Anna
    Catalan Inst Water Res ICRA, Girona, Spain.
    Groeneveld, Marloes M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Hawkes, Jeffrey A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Tranvik, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Organic Carbon Processing During Transport Through Boreal Inland Waters: Particles as Important Sites2018In: Journal of Geophysical Research - Biogeosciences, ISSN 2169-8953, E-ISSN 2169-8961, Vol. 123, no 8, p. 2412-2428Article in journal (Refereed)
    Abstract [en]

    The degradation and transformation of organic carbon (C) in inland waters result in significant CO2 emissions from inland waters. Even though most of the C in inland waters occurs as dissolved organic carbon (DOC), studies on particulate organic carbon (POC) and how it influences the overall reactivity of organic C in transport are still scarce. We sampled 30 aquatic ecosystems following an aquatic continuum including peat surface waters, streams, rivers, and lakes. We report DOC and POC degradation rates, relate degradation patterns to environmental data across these systems, and present qualitative changes in dissolved organic matter and particulate organic matter during degradation. Microbial degradation rates of POC were approximately 15 times higher compared to degradation of DOC, with POC half-lives of only 17 +/- 3 (mean +/- SE) days across all sampled aquatic ecosystems. Rapid POC decay was accompanied by a shift in particulate C: N ratios, whereas dissolved organic matter composition did not change at the time scale of incubations. The faster degradation of the POC implies a constant replenishment to sustain natural POC concentrations. We suggest that degradation of organic matter transported through the inland water continuum might occur to a large extent via transition of DOC into more rapidly cycling POC in nature, for example, triggered by light. In this way, particles would be a dominant pool of organic C processing across the boreal aquatic continuum, partially sustained by replenishment via flocculation of DOC.

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  • 28.
    Baumgart, J
    et al.
    Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden.
    Nilsson, K
    Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden.
    Stavreus Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kushnir, M M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, USA.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Androgen levels during adjuvant endocrine therapy in postmenopausal breast cancer patients2014In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 17, no 1, p. 48-54Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate plasma steroid hormone levels in postmenopausal breast cancer patients with and without adjuvant endocrine therapy and in healthy postmenopausal women.

    Methods

    Steroid hormone levels in postmenopausal breast cancer patients treated with aromatase inhibitors (n = 32) were compared with breast cancer patients treated with tamoxifen (n = 34), breast cancer patients without adjuvant endocrine therapy (n = 15), and healthy postmenopausal women (n = 56). Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, total testosterone, dihydrotestosterone, estrone and estradiol were measured using liquid chromatography-tandem mass spectrometry. Sex hormone binding globulin was measured by solid-phase chemiluminescent immunometric assays, and the free androgen index was calculated.

    Results

    Aromatase inhibitor users did not differ in dihydrotestosterone, total testosterone, androstenedione, DHEA, or free androgen index levels from healthy controls or untreated breast cancer patients. The highest total testosterone levels were found in tamoxifen-treated women, who had significantly higher plasma concentrations than both women treated with aromatase inhibitors and breast cancer patients without adjuvant treatment. Concentrations of cortisol and cortisone were significantly greater in aromatase inhibitor users as well as tamoxifen users, in comparison with healthy controls and untreated breast cancer patients. Aromatase inhibitor users had lower estrone and estradiol plasma concentrations than all other groups.

    Conclusion

    Adjuvant treatment with aromatase inhibitors or tamoxifen was associated with increased cortisol and cortisone plasma concentrations as well as decreased estradiol concentrations. Androgen levels were elevated in tamoxifen-treated women but not in aromatase inhibitor users.

  • 29. Baykut, Doan
    et al.
    Grapow, M
    Bergquist, M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Amirkhani, A
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Ivonin, I
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Reineke, D
    Grussenmeyer, T
    Håkansson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
    Zerkowski, H-R
    Baykut, G
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Molecular differentiation of ischemic and valvular heart disease by liquid chromatography/fourier transform ion cyclotron resonance mass spectrometry2006In: European Journal of Medical Research, ISSN 0949-2321, E-ISSN 2047-783X, Vol. 11, no 6, p. 221-226Article in journal (Refereed)
    Abstract [en]

    Proteomic patterns of myocardial tissue in different etiologies of heart failure were investigated using a direct analytical approach with High Performance Liquid Chromatography (HPLC)/Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Right atrial appendages from 20 patients, 10 with hemodynamically significant isolated aortic valve disease and 10 with symptomatic coronary artery disease were collected during elective cardiac surgery. After preparation of tissue samples and tryptic digestion of proteins, the peptide mixture was HPLC-separated and on-line analyzed by electrospray FT-ICR MS. Data obtained from HPLC / FT-ICR MS runs were compared for classification. To extract the classification features, the selection of best individual features was applied and the "nearest mean classifier" was used for the classification of test samples and the sample projection onto classification patterns. The pattern distribution characteristics of aortic and coronary diseases were clearly different. No interference between samples of both disease categories was registered, even if the distribution of unsupervised classified test samples were closer. Samples representing aortic valve disease showed a closer accumulation pattern of spots compared to the samples representing coronary disease, which indicated a more specific protein classification. Through selective identification of specific peptides and protein patterns with FTMS, valvular and coronary heart disease is for the first time clearly distinguished at molecular level. The described methodology could also be feasible in search for specific biomarkers in plasma or serum for diagnostic purposes.

  • 30.
    Bazoti, F N
    et al.
    GAIA Research Center, The Goulandris Natural History Museum, Greece.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, A
    GAIA Research Center, The Goulandris Natural History Museum and Pharmacy Department, Laboratory of Pharmaceutical Instrumental Analysis, University of Patras, Greece.
    Screening potential inhibitors against Alzheimer's amyloidosis using electrospray ionization mass spectrometry2008In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 74, no 9, p. 920-920Article in journal (Other academic)
  • 31. Bazoti, Fotini N.
    et al.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin E.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, Anthony
    Noncovalent interaction between amyloid-b-peptide (1-40) and oleuropein studied by electrospray ionization mass spectrometry.2006In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 17, no 4, p. 568-575Article in journal (Refereed)
    Abstract [en]

    Beta amyloid peptide (A beta) is the major proteinaceous component of senile plaques formed in Alzheimer's disease (AD) brain. The aggregation of A beta is associated with neurodegeneration, loss of cognitive ability, and premature death. It has been suggested that oxidative stress and generation of free radical species have implications in the fibrillation of A beta and its subsequent neurotoxicity. For this reason, it is proposed that antioxidants may offer a protective or therapeutic alternative against amyloidosis. This study is the first report of the formation of the noncovalent complex between A beta or its oxidized form and the natural derived antioxidant oleuropein (OE) by electrospray ionization mass spectrometry (ESI MS). ESI MS allowed the real time monitoring of the complex formation between A beta, OE, and variants thereof. Several experimental conditions, such as elevated orifice potential, low pH values, presence of organic modifier, and ligand concentration were examined, to assess the specificity and the stability of the formed noncovalent complexes.

  • 32. Bazoti, Fotini N.
    et al.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Tsarbopoulos, Anthony
    Localization of the noncovalent binding site between amyloid-beta-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry.2008In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 19, no 8, p. 1078-1085Article in journal (Refereed)
    Abstract [en]

    Abnormal accumulation and aggregation of amyloid-alpha-peptide (AM) eventually lead to the formation and cerebral deposition of amyloid plaques, the major pathological hallmark in Alzheimer's disease (AD). Oleuropein (OE), an Olea europaea L. derived polyphenol, exhibits a broad range of pharmacological properties, such as antioxidant, anti-inflammatory, and antiatherogenic, which could serve as combative mechanisms against several reported pathways involved in the pathophysiology of AD. The reported noncovalent interaction between AM and OE could imply a potential antiamyloidogenic role of the latter on the former via stabilization of its structure and prevention of the adaptation of a toxic beta-sheet conformation. The established P-sheet conformation of the AM hydrophobic carboxy-terminal region and the dependence of its toxicity and aggregational propensity on its secondary structure make the determination of the binding site between AM and OF highly important for assessing the role of the interaction. In this study, two different proteolytic digestion protocols, in conjunction with high-sensitivity electrospray ionization mass spectrometric analysis of the resulting peptide fragments, were used to determine the noncovalent binding site of OE on AM and revealed the critical regions for the interaction.

  • 33.
    Bazoti, Fotini N.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Markides, Karin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry. Analytisk kemi.
    Tsarbopoulos, Anthony
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Localization of the Noncovalent Binding Site Between Amyloid-B-Peptide and Oleuropein Using Electrospray Ionization FT-ICR Mass Spectrometry2008In: J. Am. Soc. Mass. Spectrom., no 19, p. 1078-1085Article in journal (Refereed)
  • 34.
    Bazoti, Fotini N
    et al.
    GAIA Research Center, The Goulandris Natural History Museum and Department of Pharmacy, Laboratory of Instrumental Analysis, University of Patras, Greece.
    Tsarbopoulos, Anthony
    GAIA Research Center, The Goulandris Natural History Museum and Department of Pharmacy, Laboratory of Instrumental Analysis, University of Patras, Greece.
    Markides, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Study of the non-covalent interaction between amyloid-beta-peptide and melatonin using electrospray ionization mass spectrometry2005In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 40, no 2, p. 182-192Article in journal (Refereed)
    Abstract [en]

    Oxidative stress and unregulated immune response are believed to play a key role in the processes inherent to Alzheimer's disease (AD). The fact that free radicals can result in neurodegeneration suggests that actions against reactive oxygen species may be beneficial in treating and preventing AD. In the light of the suggested link between oxidative stress and AD, it is proposed that antioxidants and, even more, endogenous antioxidants may offer a therapeutic regime for protection against the risk of this disease. For this reason, the formation of non-covalent complexes between amyloid-beta-peptide (A beta) or its oxidized forms and melatonin was studied by quadrupole and Fourier transform ion cyclotron resonance electrospray ionization mass spectrometry. The stability of the non-covalent complex was examined under several experimental conditions, such as orifice voltage, pH, presence of organic modifier, concentration and time. Two different digestion protocols combined with mass spectrometric analysis of the resulting peptide fragments were employed in order to locate the binding site of melatonin in A beta.

  • 35. Bazoti, Fotini N.
    et al.
    Tsarbopoulos, Anthony
    Markides, Karin E.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Analytisk kemi.
    Bergquist, Jonas
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Analytisk kemi.
    Study of the non-covalent interaction between amyloid-b-peptide and melatonin using electrospray ionization mass spectrometry2005In: Journal of Mass Spectrometry, no 40, p. 182-192Article in journal (Refereed)
    Abstract [en]

    Oxidative stress and unregulated immune response are believed to play a key role in the processes inherent to Alzheimer's disease (AD). The fact that free radicals can result in neurodegeneration suggests that actions against reactive oxygen species may be beneficial in treating and preventing AD. In the light of the suggested link between oxidative stress and AD, it is proposed that antioxidants and, even more, endogenous antioxidants may offer a therapeutic regime for protection against the risk of this disease. For this reason, the formation of non-covalent complexes between amyloid-b-peptide (Ab) or its oxidized forms and melatonin was studied by quadrupole and Fourier transform ion cyclotron resonance electrospray ionization mass spectrometry. The stability of the non-covalent complex was examined under several experimental conditions, such as orifice voltage, pH, presence of organic modifier, concentration and time. Two different digestion protocols combined with mass spectrometric analysis of the resulting peptide fragments were employed in order to locate the binding site of melatonin in Ab.

  • 36.
    Berglund, Erik
    et al.
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Ubhayasekera, Sarojini J.K.A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karlsson, Fredrik
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Akcakaya, Pinar
    Department of Oncology-Pathology, Cancer Center Karolinska Institutet.
    Aluthgedara, Warunika
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ahlen, Jan
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Fröbom, Robin
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet.
    Nilsson, Inga-Lena
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Lui, Weng-Onn
    Department of Oncology-Pathology, Cancer Center Karolinska Institutet.
    Larsson, Catharina
    Department of Oncology-Pathology, Cancer Center Karolinska Institutet.
    Zedenius, Jan
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bränström, Robert
    Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet AND Department of Breast and Endocrine Surgery, Karolinska University Hospital.
    Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells.2014In: Anti-Cancer Drugs, ISSN 0959-4973, E-ISSN 1473-5741, Vol. 25, no 4, p. 415-22Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract. In most GISTs, the underlying mechanism is a gain-of-function mutation in the KIT or the PDGFRA gene. Imatinib is a tyrosine kinase inhibitor that specifically blocks the intracellular ATP-binding sites of these receptors. A correlation exists between plasma levels of imatinib and progression-free survival, but it is not known whether the plasma concentration correlates with the intracellular drug concentration. We determined intracellular imatinib levels in two GIST cell lines: the imatinib-sensitive GIST882 and the imatinib-resistant GIST48. After exposing the GIST cells to imatinib, the intracellular concentrations were evaluated using LC-MS (TOF). The concentration of imatinib in clinical samples from three patients was also determined to assess the validity and reliability of the method in the clinical setting. Determination of imatinib uptake fits within detection levels and values are highly reproducible. The GIST48 cells showed significantly lower imatinib uptake compared with GIST882 in therapeutic doses, indicating a possible difference in uptake mechanisms. Furthermore, imatinib accumulated in the tumor tissues and showed intratumoral regional differences. These data show, for the first time, a feasible and reproducible technique to measure intracellular imatinib levels in experimental and clinical settings. The difference in the intracellular imatinib concentration between the cell lines and clinical samples indicates that drug transporters may contribute toward resistance mechanisms in GIST cells. This highlights the importance of further clinical studies to quantify drug transporter expression and measure intracellular imatinib levels in GIST patients.

  • 37.
    Bergman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingvar Eidhammer, Harald Barsnes, Geir Egil Eide, and Lennart Martens:: Computational and statistical methods for protein quantification by mass spectrometry2014In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 6, p. 1575-1576Article, book review (Refereed)
  • 38.
    Bergman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Recent developments in proteomic methods and disease biomarkers2014In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 139, p. 3836-3851Article in journal (Refereed)
    Abstract [en]

    Proteomic methodologies for identification and analysis of biomarkers have gained more attention during recent years and have evolved rapidly. Identification and detection of disease biomarkers are important to foresee outbreaks of certain diseases thereby avoiding surgery and other invasive and expensive medical treatments for patients. Thus, more research into discovering new biomarkers and new methods for faster and more accurate detection is needed. It is often difficult to detect and measure biomarkers because of their low concentrations and the complexity of their respective matrices. Therefore it is hard to find and validate methods for accurate screening methods suitable for clinical use. The most recent developments during the last three years and also some historical considerations of proteomic methodologies for identification and validation of disease biomarkers are presented in this review.

  • 39.
    Bergman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Shevchenko, Denys
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Approaches for the analysis of low molecular weight compounds with laser desorption/ionization techniques and mass spectrometry2014In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 1, p. 49-61Article, review/survey (Refereed)
    Abstract [en]

    This review summarizes various approaches for the analysis of low molecular weight (LMW) compounds by different laser desorption/ionization mass spectrometry techniques (LDI-MS). It is common to use an agent to assist the ionization, and small molecules are normally difficult to analyze by, e.g., matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) using the common matrices available today, because the latter are generally small organic compounds themselves. This often results in severe suppression of analyte peaks, or interference of the matrix and analyte signals in the low mass region. However, intrinsic properties of several LDI techniques such as high sensitivity, low sample consumption, high tolerance towards salts and solid particles, and rapid analysis have stimulated scientists to develop methods to circumvent matrix-related issues in the analysis of LMW molecules. Recent developments within this field as well as historical considerations and future prospects are presented in this review.

  • 40.
    Bergman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Thapper, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Styring, Stenbjorn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Shevchenko, Denys
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Quantitative determination of the Ru(bpy)(3)(2+) cation in photochemical reactions by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry2014In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 6, no 21, p. 8513-8518Article in journal (Refereed)
    Abstract [en]

    The coordination compound of Ru(II) with three 2,2'-bipyridine ligands possesses a potent photosensitization capacity for electron- and energy-transfer processes. In combination with salts of peroxydisulfate acid as sacrificial electron acceptors, Ru(bpy)(3)(2+) is widely used for photocatalytic oxidative transformations in organic synthesis and water splitting. The drawback of this system is that bipyridine degrades under the resulting strongly oxidative conditions, the concentration of Ru(bpy)(3)(2+) diminishes, and the photocatalytic reaction eventually stops. A commonly employed assay for the determination of Ru(bpy)(3)(2+), UV-Vis spectroscopy, has low selectivity and does not distinguish between the intact complex and its decayed forms. Here, we report a matrix assisted laser desorption/ionisation mass spectrometric method for the quantitative analysis of Ru(bpy)(3)(2+) in photochemical reaction mixtures. The developed method was successfully used for the determination of intact Ru(bpy)(3)(2+) during the course of the water photooxidation reaction. The significant difference between the results of MALDI MS and UV-Vis analyses was observed.

  • 41.
    Bergquist, J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    From MALDI-TOF MS to Two Dimensional CE-FTICR-MS of Proteins in Spinal Fluid2002In: Molecular Testing in Laboratory Medicine, 2002, p. 171-172Chapter in book (Other academic)
  • 42.
    Bergquist, J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    From molecule to man - using electrospray Fourier Transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) in proteomics2003In: ISMAS Silver Jubilee Symposium on Mass Spectrometry, 2003Chapter in book (Other academic)
  • 43.
    Bergquist, J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    FTICR mass spectrometry in proteomics2003In: Current Opinion in Molecular Therapeutics, no 5, p. 310-314Article in journal (Refereed)
  • 44.
    Bergquist, J
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Andersen, O
    Westman, A
    Rapid method to characterize mutations in transthyretin in cerebrospinal fluid from familial amyloidotic polyneuropathy patients by use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry2000In: Clin. Chem., Vol. 46, no 9, p. 1293-1300Article in journal (Refereed)
  • 45.
    Bergquist, J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Ekman, R.
    The dynamics of the cell nucleus - Lymphocyte nuclei associated peptides studied by mass spectrometry and future peptidomic aspects2002In: Mass spectrometry and Hyphenated Techniques in Neuropeptide Research, John Wiley & Sons, N.Y. , 2002, Vol. Chapter 21, p. 519-553Chapter in book (Refereed)
  • 46.
    Bergquist, J
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Gobom, J
    Blomberg, A
    Roepstorff, P
    Ekman, R
    Identification of nuclei associated proteins by 2D-gel electrophoresis and mass spectrometry2001In: J. Neurosci. Meth., no 109, p. 3-11Article in journal (Refereed)
  • 47.
    Bergquist, J
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Ohlsson, B
    Tarkowski, A
    Nuclear factor-kB is involved in the catecholaminergic suppression of immunocompetent cells2000In: Neuroimmodulation, Vol. 917, p. 281-289Article in journal (Refereed)
  • 48.
    Bergquist, J.
    et al.
    ION PHYSICS. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Palmblad, M.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Wetterhall, M., Håkansson, P., Markides, K.E.
    Peptide mapping of proteins in human body fluids using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry2002In: Mass. Spectrom. Reviews, no 21, p. 2-15Article in journal (Refereed)
  • 49.
    Bergquist, J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Sciubisz, A.
    Kaczor, A.
    Silberring, J.
    Catecholamines and methods for their identification and quantitation in biological tissues and fluids2002In: J. Neurosci. Meth., no 113, p. 1-13Article in journal (Refereed)
  • 50.
    Bergquist, J.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Träskman-Bendz, L.
    Lindström, M.B.
    Ekman, R.
    Suicide-attempters having immunoglobulin G with affinity for dopamine in cerebrospinal fluid2002In: European Neuropsychopharmacology, no 12, p. 153-158Article in journal (Refereed)
1234567 1 - 50 of 497
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