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  • 1.
    Adler, Stephan O.
    et al.
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
    Spiesser, Thomas W.
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
    Uschner, Friedemann
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany; Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Sachsen, Germany.
    Münzner, Ulrike
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany; Laboratory of Cell Systems, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
    Hahn, Jens
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
    Krantz, Marcus
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
    Klipp, Edda
    Institute of Biology, Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany.
    A yeast cell cycle model integrating stress, signaling, and physiology2022In: FEMS yeast research (Print), ISSN 1567-1356, E-ISSN 1567-1364, Vol. 22, no 1, article id foac026Article in journal (Refereed)
    Abstract [en]

    The cell division cycle in eukaryotic cells is a series of highly coordinated molecular interactions that ensure that cell growth, duplication of genetic material, and actual cell division are precisely orchestrated to give rise to two viable progeny cells. Moreover, the cell cycle machinery is responsible for incorporating information about external cues or internal processes that the cell must keep track of to ensure a coordinated, timely progression of all related processes. This is most pronounced in multicellular organisms, but also a cardinal feature in model organisms such as baker's yeast. The complex and integrative behavior is difficult to grasp and requires mathematical modeling to fully understand the quantitative interplay of the single components within the entire system. Here, we present a self-oscillating mathematical model of the yeast cell cycle that comprises all major cyclins and their main regulators. Furthermore, it accounts for the regulation of the cell cycle machinery by a series of external stimuli such as mating pheromones and changes in osmotic pressure or nutrient quality. We demonstrate how the external perturbations modify the dynamics of cell cycle components and how the cell cycle resumes after adaptation to or relief from stress.

  • 2.
    Ahlberg, Emelie
    et al.
    Department ofBiomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
    Jenmalm, Maria C.
    Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
    Karlsson, Anders
    Nanoxis Consulting AB, Gothenburg, Sweden.
    Karlsson, Roger
    Nanoxis Consulting AB, Gothenburg, Sweden; Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tingö, Lina
    Örebro University, School of Medical Sciences. Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
    Proteome characterization of extracellular vesicles from human milk: Uncovering the surfaceome by a lipid-based protein immobilization technology2024In: Journal of extracellular biology, E-ISSN 2768-2811, Vol. 3, no 11, article id e70020Article in journal (Refereed)
    Abstract [en]

    Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex fluid is rich in extracellular vesicles (EVs). Here, we have applied a microfluidic technology, lipid-based protein immobilization (LPI) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterize the proteome of human milk EVs. Mature milk from six mothers was subjected to EV isolation by ultracentrifugation followed by size exclusion chromatography. Three of the samples were carefully characterized; suggesting a subset enriched by small EVs. The EVs were digested by trypsin in an LPI flow cell and in-solution digestion, giving rise to two fractions of peptides originating from the surface proteome (LPI fraction) or the complete proteome (in-solution digestion). LC-MS/MS recovered peptides corresponding to 582 proteins in the LPI fraction and 938 proteins in the in-solution digested samples; 400 of these proteins were uniquely found in the in-solution digested samples and were hence denoted "cargo proteome". GeneOntology overrepresentation analysis gave rise to distinctly different functional predictions of the EV surfaceome and the cargo proteome. The surfaceome tends to be overrepresented in functions and components of relevance for the immune system, while the cargo proteome primarily seems to be associated with EV biogenesis.

  • 3.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Persson, B.
    cDepartment of Radiology, Karolinska Hospital, Stockholm, Sweden.
    Bindslev, L.
    Department of Anesthesiology and Intensive Care, Karolinska Hospital, Department of Anesthesiology and Intensive Care, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Intestinal amino acid content in critically ill patients1995In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 19, no 4, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of the study was to determine the concentrations of free amino acids and the total protein content of the human intestinal mucosa during critical illness. Methods: The free amino acid and protein concentrations in endoscopically obtained biopsy specimens from the duodenum and the distal colonic segments were determined on 19 critically ill patients. The free amino acids were separated by ion exchange chromatography and detected by fluorescence, and the protein content was quantified by the method of Lowry. Results: In general, the typical amino acid pattern of the intestinal mucosa was seen, with very high levels of taurine, aspartate and glutamic acid. The main difference, as compared to a reference series of healthy subjects, was the elevated glutamine concentration of the duodenal mucosa. This amino acid was unaltered in the descending colon and depressed in the rectum. At the same time, the glutamatic acid concentrations were unaltered, suggesting that the degradation of glutamine was not increased in the septic state of the majority of the patients studied. Phenylalanine and the two branched-chain amino acids, valine and leucine, were elevated in the duodenal mucosa, and in the colonic mucosa, methionine and phenylalanine were elevated; otherwise, all the other individual amino acids were unaltered or depressed. Conclusions: The alterations seen in mucosal free amino acid and protein concentrations in connection with critical illness are different in many respects and contrast with the findings seen after starvation or moderate surgical trauma.

  • 4.
    Alijagic, Andi
    et al.
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Gaglio, Daniela
    SYSBIO.IT, Centre of Systems Biology, University of Milano-Bicocca, Milano, Italy; Istituto di Bioimmagini e Fisiologia Molecolare (IBFM), Consiglio Nazionale delle Ricerche, Segrate, Milano, Italy.
    Napodano, Elisabetta
    SYSBIO.IT, Centre of Systems Biology, University of Milano-Bicocca, Milano, Italy.
    Russo, Roberta
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Costa, Caterina
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Benada, Oldřich
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Kofroňová, Olga
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Pinsino, Annalisa
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Titanium dioxide nanoparticles temporarily influence the sea urchin immunological state suppressing inflammatory-relate gene transcription and boosting antioxidant metabolic activity2020In: Journal of Hazardous Materials, ISSN 0304-3894, E-ISSN 1873-3336, Vol. 384, article id 121389Article in journal (Refereed)
    Abstract [en]

    Titanium dioxide nanoparticles (TiO2NPs) are revolutionizing biomedicine due to their potential application as diagnostic and therapeutic agents. However, the TiO2NP immune-compatibility remains an open issue, even for ethical reasons. In this work, we investigated the immunomodulatory effects of TiO2NPs in an emergent proxy to human non-mammalian model for in vitro basic and translational immunology: the sea urchin Paracentrotus lividus. To highlight on the new insights into the evolutionarily conserved intracellular signaling and metabolism pathways involved in immune-TiO2NP recognition/interaction we applied a wide-ranging approach, including electron microscopy, biochemistry, transcriptomics and metabolomics. Findings highlight that TiO2NPs interact with immune cells suppressing the expression of genes encoding for proteins involved in immune response and apoptosis (e.g. NF-κB, FGFR2, JUN, MAPK14, FAS, VEGFR, Casp8), and boosting the immune cell antioxidant metabolic activity (e.g. pentose phosphate, cysteine-methionine, glycine-serine metabolism pathways). TiO2NP uptake was circumscribed to phagosomes/phagolysosomes, depicting harmless vesicular internalization. Our findings underlined that under TiO2NP-exposure sea urchin innate immune system is able to control inflammatory signaling, excite antioxidant metabolic activity and acquire immunological tolerance, providing a new level of understanding of the TiO2NP immune-compatibility that could be useful for the development in Nano medicines. 

  • 5.
    Andersson, M. R.
    et al.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Samyn, Dieter R.
    Örebro University, School of Medical Sciences. Örebro University Hospital. School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Persson, B. L.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Belgium; Department of Molecular Microbiology, Leuven-Heverlee, Flanders, Belgium.
    Mutational analysis of conserved glutamic acids of Pho89, a Saccharomyces cerevisiae high-affinity inorganic phosphate:Na + symporter2012In: Biologia, ISSN 0006-3088, E-ISSN 1336-9563, Vol. 67, no 6, p. 1056-1061Article in journal (Refereed)
    Abstract [en]

    In Saccharomyces cerevisiae, the high-affinity phosphate transport system comprises the Pho84 and Pho89 permeases. The Pho89 permease catalyzes import of inorganic phosphate in a symport manner by utilizing Na + ions as co-solute. We have addressed the functional importance of two glutamic acid residues at positions 55 and 491. Both residues are highly conserved amongst members of the inorganic phosphate transporter (PiT) family, which might be an indication of functional importance. Moreover, both residues have been shown to be of critical importance in the hPit2 transporter. We have created site-directed mutations of both E55 and E491 to lysine and glutamine. We observed that in all four cases there is a dramatic impact on the transport activity, and thus it seems that they indeed are of functional importance. Following these observations, we addressed the membrane topology of this protein by using several prediction programs. TOPCONS predicts a 7-5 transmembrane segment organization, which is the most concise topology as compared to the hPiT2 transporter. By understanding the functionality of these residues, we are able to correlate the Pho89 topology to that of the hPiT2, and can now further analyze residues which might play a role in the transport activity. © 2012 Versita Warsaw and Springer-Verlag Wien.

  • 6.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    CHIMERIC MOMP ANTIGEN2015Patent (Other (popular science, discussion, etc.))
    Download full text (pdf)
    Patent
  • 7.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Chimeric MOMP antigen2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.

    Download full text (pdf)
    Patent
  • 8.
    Arvidsson, A. K.
    et al.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Rupp, E.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Nånberg, Eewa
    Department of Pathology, University Hospital, Uppsala, Sweden.
    Downward, J.
    Signal Transduction Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
    Rönnstrand, L.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Wennström, S.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Schlessinger, J.
    Department of Pharmacology, New York University Medical Center, New York, NY, USA .
    Heldin, C. H.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Claesson-Welsh, L.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation1994In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 14, no 10, p. 6715-6726Article in journal (Refereed)
    Abstract [en]

    Ligand stimulation of the platelet-derived growth factor (PDGF) beta-receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation of the intracellular part of the receptor. The autophosphorylated tyrosine residues mediate interactions with downstream signal transduction molecules and thereby initiate different signalling pathways. A pathway leading to activation of the GTP-binding protein Ras involves the adaptor molecule GRB2. Here we show that Tyr-716, a novel autophosphorylation site in the PDGF beta-receptor kinase insert, mediates direct binding of GRB2 in vitro and in vivo. In a panel of mutant PDGF beta-receptors, in which Tyr-716 and the previously known autophosphorylation sites were individually mutated, only PDGFR beta Y716F failed to bind GRB2. Furthermore, a synthetic phosphorylated peptide containing Tyr-716 bound GRB2, and this peptide specifically interrupted the interaction between GRB2 and the wild-type receptor. In addition, the Y716(P) peptide significantly decreased the amount of GTP bound to Ras in response to PDGF in permeabilized fibroblasts as well as in porcine aortic endothelial cells expressing transfected PDGF beta-receptors. The mutant PDGFR beta Y716F still mediated activation of mitogen-activated protein kinases and an increased DNA synthesis in response to PDGF, indicating that multiple signal transduction pathways transduce mitogenic signals from the activated PDGF beta-receptor.

  • 9.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Paulsen, Katrine M.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Pedersen, Benedikte N.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Bø-Granquist, Erik G.
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Vikse, Rose
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Stuen, Snorre
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Andersson, Sören
    Folkhälsomyndigheten, Public Health Agency of Sweden, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andreassen, Åshild K.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana 2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 10, article id 1667Article in journal (Refereed)
    Abstract [en]

    Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection. 

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    bilaga
  • 10.
    Asnake, Solomon
    et al.
    Örebro University, School of Science and Technology.
    Modig, Carina
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Species differences in ligand interaction and activation of estrogen receptors in fish and human2019In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 195, article id 105450Article in journal (Refereed)
    Abstract [en]

    Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (β) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERβ and seabream ERβ2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.

  • 11.
    Aura, Anna-Marja
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland.
    Gopalacharyulu, Peddinti
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Bounsaythip, Catherine
    University of Helsinki, Helsinki, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Oksman-Caldentey, Kirsi-Marja
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Drug metabolome of the simvastatin formed by human intestinal microbiota in vitro2011In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 7, no 2, p. 437-446Article in journal (Refereed)
    Abstract [en]

    The human colon contains a diverse microbial population which contributes to degradation and metabolism of food components. Drug metabolism in the colon is generally poorly understood. Metabolomics techniques and in vitro colon models are now available which afford detailed characterization of drug metabolites in the context of colon metabolism. The aim of this work was to identify novel drug metabolites of Simvastatin (SV) by using an anaerobic human in vitro colon model at body temperature coupled with systems biology platform, excluding the metabolism of the host liver and intestinal epithelia. Comprehensive two-dimensional gas chromatography with a time-of-flight mass spectrometry (GC×GC-TOFMS) was used for the metabolomic analysis. Metabolites showing the most significant differences in the active faecal suspension were elucidated in reference with SV fragmentation and compared with controls: inactive suspension or buffer with SV, or with active suspension alone. Finally, time courses of selected metabolites were investigated. Our data suggest that SV is degraded by hydrolytic cleavage of methylbutanoic acid from the SV backbone. Metabolism involves demethylation of dimethylbutanoic acid, hydroxylation/dehydroxylation and β-oxidation resulting in the production of 2-hydroxyisovaleric acid (3-methyl-2-hydroxybutanoic acid), 3-hydroxybutanoic acid and lactic acid (2-hydroxypropanoic acid), and finally re-cyclisation of heptanoic acid (possibly de-esterified and cleaved methylpyranyl arm) to produce cyclohexanecarboxylic acid. Our study elucidates a pathway of colonic microbial metabolism of SV as well as demonstrates the applicability of the in vitro colon model and metabolomics to the discovery of novel drug metabolites from drug response profiles.

  • 12.
    Babazadeh, Roja
    et al.
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Moghadas Jafari, Soode
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Zackrisson, Martin
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Blomberg, Anders
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Hohmann, Stefan
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Warringer, Jonas
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Krantz, Marcus
    Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    TheAshbya gossypiiEF-1αpromoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae2011In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 585, no 24, p. 3907-3913Article in journal (Refereed)
    Abstract [en]

    Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone. 

  • 13.
    Baksi, Shounak
    et al.
    Causality Biomodels, Kerala Technology Innovation Zone, Cochin, India.
    Pradhan, Ajay
    Örebro University, School of Science and Technology.
    Thyroid hormone: sex-dependent role in nervous system regulation and disease2021In: Biology of Sex Differences, ISSN 2042-6410, Vol. 12, no 1, article id 25Article, review/survey (Refereed)
    Abstract [en]

    Thyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone level in the body can lead to nervous system-related problems linked to cognition, visual attention, visual processing, motor skills, language, and memory skills. TH has also been associated with neuropsychiatric disorders including schizophrenia, bipolar disorder, anxiety, and depression. Males and females display sex-specific differences in neuronal signaling. Steroid hormones including testosterone and estrogen are considered to be the prime regulators for programing the neuronal signaling in a male- and female-specific manner. However, other than steroid hormones, TH could also be one of the key signaling molecules to regulate different brain signaling in a male- and female-specific manner. Thyroid-related diseases and neurological diseases show sex-specific incidence; however, the molecular mechanisms behind this are not clear. Hence, it will be very beneficial to understand how TH acts in male and female brains and what are the critical genes and signaling networks. In this review, we have highlighted the role of TH in nervous system regulation and disease outcome and given special emphasis on its sex-specific role in male and female brains. A network model is also presented that provides critical information on TH-regulated genes, signaling, and disease.

  • 14.
    Balaz, Martina
    et al.
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Sundberg, Mark
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Persson, Malin
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Kvassman, Jan
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Månsson, Alf
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Effects of surface adsorption on catalytic activity of heavy meromyosin studied using a fluorescent ATP analogue2007In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 46, no 24, p. 7233-7251Article in journal (Refereed)
    Abstract [en]

    Biochemical studies in solution and with myosin motor fragments adsorbed to surfaces (in vitro motility assays) are invaluable for elucidation of actomyosin function. However, there is limited understanding of how surface adsorption affects motor properties, e.g., catalytic activity. Here we address this issue by comparing the catalytic activity of heavy meromyosin (HMM) in solution and adsorbed to standard motility assay surfaces [derivatized with trimethylchlorosilane (TMCS)]. For these studies we first characterized the interaction of HMM and actomyosin with the fluorescent ATP analogue adenosine 5'-triphosphate Alexa Fluor 647 2'- (or 3'-) O-(N-(2-aminoethyl)urethane) hexa(triethylammonium) salt (Alexa-ATP). The data suggest that Alexa-ATP is hydrolyzed by HMM in solution at a slightly higher rate than ATP but with a generally similar mechanism. Furthermore, Alexa-ATP is effective as a fuel for HMM-propelled actin filament sliding. The catalytic activity of HMM on TMCS surfaces was studied using (1) Alexa-ATP in total internal reflection fluorescence (TIRF) spectroscopy experiments and (2) Alexa-ATP and ATP in HPLC-aided ATPase measurements. The results support the hypothesis of different HMM configurations on the surface. However, a dominant proportion of the myosin heads were catalytically active, and their average steady-state hydrolysis rate was slightly higher (with Alexa-ATP) or markedly higher (with ATP) on the surface than in solution. The results are discussed in relation to the use of TMCS surfaces and Alexa-ATP for in vitro motility assays and single molecule studies. Furthermore, we propose a novel TIRF microscopy method to accurately determine the surface density of catalytically active myosin motors.

  • 15.
    Barnes, Paul W.
    et al.
    Loyola University, New Orleans, USA.
    Morales, Luis Orlando
    Örebro University, School of Science and Technology.
    Robson, T. M.
    University of Helsinki, Helsinki, Finland.
    The importance and direction of current and future plant-UV research2018In: UV4Plants Bulletin, ISSN 2343-323X, Vol. 2, p. 19-32Article in journal (Refereed)
    Abstract [en]

    Background

    To stimulate how to move the field of plant-UV research forward, and create a coherent framework to highlight valuable future directions in plant UV research we had a group discussion of the most prescient questions and how to address them.

    The following sections are broken-down into those from the molecular, biochemical and physiological discussions followed by those from the ecological and plant production discussions. In each case, first basic research questions are considered and then applications and methodological considerations put forward. Finally, some common ground bringing together the two perspectives is proposed, aimed at solving scaling problems and ways in which the UV4Plants network might be put to good use.

  • 16.
    Basheer, Shabana
    et al.
    Department of Biotechnology, Lund University, Lund, Sweden; School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Samyn, Dieter R.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Hedström, Martin
    Department of Biotechnology, Lund University, Lund, Sweden.
    Thakur, Munna Singh
    Department of Fermentation, Technology and Bioengineering, Central Food Technology Research Institute, Mysore, India.
    Persson, Bengt L.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden; Lab. of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit, Leuven, Belgium; Department of Molecular Microbiology, VIB, Leuven-Heverlee, Flanders, Belgium.
    Mattiasson, Bo
    Department of Biotechnology, Lund University, Lund, Sweden.
    A membrane protein based biosensor: use of a phosphate--H+ symporter membrane protein (Pho84) in the sensing of phosphate ions2011In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 27, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    A label free biosensor for direct detection of inorganic phosphate based on potential-step capacitance measurements has been developed. The high-affinity Pho84 plasma membrane phosphate/proton symporter of Saccharomyces cerevisiae was used as a sensing element. Heterologously expressed and purified Pho84 protein was immobilized on a self-assembled monolayer (SAM) on a capacitance electrode. Changes in capacitance were recorded upon exposure to phosphate compared to the control substance, phosphate analogue methylphosphonate. Hence, even without the explicit use of lipid membranes, the Pho84 membrane protein could retain its capacity of selective substrate binding, with a phosphate detection limit in the range of the apparent in vivo K(m). A linear increase in capacitance was monitored in the phosphate concentration range of 5-25 μM. The analytical response of the capacitive biosensor is in agreement with that the transporter undergoes significant conformational changes upon exposure to inorganic phosphate, while exposure to the analogue only causes minor responses.

  • 17.
    Bereketoglu, Ceyhun
    et al.
    Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Iskenderun Technical University, Hatay, Turkey.
    Nacar, Gozde
    Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.
    Sari, Tugba
    Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.
    Mertoglu, Bulent
    Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.
    Pradhan, Ajay
    Örebro University, School of Science and Technology. Biology, The Life Science Center.
    Transcriptomic analysis of nonylphenol effect on Saccharomyces cerevisiae2021In: PeerJ, E-ISSN 2167-8359, Vol. 9, article id e10794Article in journal (Refereed)
    Abstract [en]

    Nonylphenol (NP) is a bioaccumulative environmental estrogen that is widely used as a nonionic surfactant. We have previously examined short-term effects of NP on yeast cells using microarray technology. In the present study, we investigated the adaptive response of Saccharomyces cerevisiae BY4742 cells to NP exposure by analyzing genome-wide transcriptional profiles using RNA-sequencing. We used 2 mg/L NP concentration for 40 days of exposure. Gene expression analysis showed that a total of 948 genes were differentially expressed. Of these, 834 genes were downregulated, while 114 genes were significantly upregulated. GO enrichment analysis revealed that 369 GO terms were significantly affected by NP exposure. Further analysis showed that many of the differentially expressed genes were associated with oxidative phosphorylation, iron and copper acquisition, autophagy, pleiotropic drug resistance and cell cycle progression related processes such as DNA and mismatch repair, chromosome segregation, spindle checkpoint activity, and kinetochore organization. Overall, these results provide considerable information and a comprehensive understanding of the adaptive response to NP exposure at the gene expression level.

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    Transcriptomic analysis of nonylphenol effect on Saccharomyces cerevisiae
  • 18.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine.
    Ramström, Sofia
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Kardeby, Caroline
    Örebro University, School of Medical Sciences.
    Hultenby, Kjell
    Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm.
    Göthlin Eremo, Anna
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Sihlbom, Carina
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Bergström, Jörgen
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Palmblad, Jan
    Åström, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine.
    Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome2021In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 106, no 11, p. 2947-2959Article in journal (Refereed)
    Abstract [en]

    In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet α- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change ≥±1.2, q< .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and α-granule release and fibrinogen binding in response to ligation of receptors for ADP, the thrombin receptor PAR4 and the collagen receptor GPVI. Significant reductions of a number of α-granule proteins overlapped with a previous platelet proteomics investigation in the inherited macrothrombocytopenia gray platelet syndrome (GPS). In contrast, Ca2+ transporter proteins that facilitate dense granule release were downregulated in XLTT but upregulated in GPS. Ingenuity Pathway Analysis showed altered Coagulation System and Protein Ubiquitination pathways in the XLTT platelets. Collectively, the results revealed protein and functional alterations affecting platelet α- and dense granules in XLTT, probably contributing to bleeding.

  • 19. Björkblom, Carina
    et al.
    Olsson, Per-Erik
    Örebro University, Department of Natural Sciences.
    Katsiadaki, I
    Wiklund, T
    Estrogen- and androgen-sensitive bioassays based on primary cell and tissue slice cultures from three-spined stickleback (Gasterosteus aculeatus)2007In: Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, ISSN 1532-0456, E-ISSN 1878-1659, Vol. 146, no 3, p. 431-442Article in journal (Refereed)
    Abstract [en]

    Endocrine disrupting compounds are chemicals that may interfere with the endocrine system causing severe effects in organisms. The three-spined stickleback (Gasterosteus aculeatus L.) offers a potential for the assessment of endocrine disruption caused by a) estrogenic xenobiotics through the estrogen-dependent protein vitellogenin and b) androgenic xenobiotics through the androgen-dependent protein spiggin. The stickleback is presently the only known fish species with a quantifiable androgen and anti-androgen biomarker endpoint. In the current study, hepatocyte and kidney primary cell cultures and liver and kidney tissue slice cultures were prepared and used for detecting estrogenic or androgenic activity in vitro through the action of hormones or municipal sewage water. The results indicate that stickleback male hepatocyte cultures are suitable in detecting estrogenic activity and stickleback female kidney tissue slice cultures in detecting androgenic activity. The tested sewage water showed high estrogenic activity but no significant androgenic activity. Primary cell and tissue slice cultures isolated from the three-spined stickleback will allow simultaneously screening in vitro for potential estrogenic and androgenic activity of complex samples.

  • 20.
    Björnberg, Anna
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Inhibition of the growth of grain-storage molds in vitro by the yeast Pichia anomala (Hansen) Kurtzman1993In: Canadian journal of microbiology (Print), ISSN 0008-4166, E-ISSN 1480-3275, Vol. 39, no 6, p. 623-628Article in journal (Refereed)
    Abstract [en]

    The potential Use Of yeasts to control grain-storage molds was evaluated by coculturing the yeast Pichia anomala with Penicillium roqueforti and Aspergillus candidus on agar plates, using different temperatures, water activities (a(w)), and nutrient concentrations. Addition of 10 ppm cycloheximide to malt-extract agar inhibited Pichia anomala completely without affecting mold growth, making it possible to quantify the inhibition as a reduction in colony-forming units (cfu). For A. candidus, numbers of cfu and hyphal lengths were reduced at an initial yeast concentration of 10(4) cells/plate and reduced below detection limit at 10(8) cells/plate. A clear reduction in growth of Penicillium roqueforti was only observed at 10(8) yeast cells/plate. The antagonistic effect was generally more pronounced at low (6, 15-degrees-C) and high (30, 37-degrees-C) temperatures than at ambient ones. Pichia anomala inhibited growth of both molds more strongly in a substrate-rich medium than in a medium with a low substrate content. In water agar (low substrate concentration) the degree of inhibition of Penicillium roqueforti was larger at 0.96 a(w) than at 0.98 a(w).

  • 21.
    Blanc, Mélanie
    et al.
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Kukučka, Petr
    Örebro University, School of Science and Technology.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Keiter, Steffen
    Örebro University, School of Science and Technology.
    Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)2017In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 590-591, p. 249-257Article in journal (Refereed)
    Abstract [en]

    Perfluorooctane sulfonic acid (PFOS) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5 μg/L of PCB126 alone, in the presence of 25 mg/L of PFOS, 15.7 mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24 h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78 h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126 + PFOS + PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126 + PFHxA and to PCB126 + PFOS + PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126 + PFOS + PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.

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    fulltext
  • 22.
    Brandt, Erik G.
    et al.
    Theoretical Biological Physics, Department of Theoretical Physics, Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden .
    Hellgren, Mikko
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden .
    Brinck, Tore
    Department of Physical Chemistry, Royal Institute of Technology, Stockholm, Sweden .
    Bergman, Tomas
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden .
    Edholm, Olle
    Theoretical Biological Physics, Department of Theoretical Physics, Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden .
    Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site2009In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 11, no 6, p. 975-983Article in journal (Refereed)
    Abstract [en]

    The binding of zinc (Zn) ions to proteins is important for many cellular events. The theoretical and computational description of this binding (as well as that of other transition metals) is a challenging task. In this paper the binding of the Zn ion to four cysteine residues in the structural site of horse liver alcohol dehydrogenase (HLADH) is studied using a synthetic peptide mimic of this site. The study includes experimental measurements of binding constants, classical free energy calculations from molecular dynamics (MD) simulations and quantum mechanical (QM) electron structure calculations. The classical MD results account for interactions at the molecular level and reproduce the absolute binding energy and the hydration free energy of the Zn ion with an accuracy of about 10%. This is insufficient to obtain correct free energy differences. QM correction terms were calculated from density functional theory (DFT) on small clusters of atoms to include electronic polarisation of the closest waters and covalent contributions to the Zn–S coordination bond. This results in reasonably good agreement with the experimentally measured binding constants and Zn ion hydration free energies in agreement with published experimental values. The study also includes the replacement of one cysteine residue to an alanine. Simulations as well as experiments showed only a small effect of this upon the binding free energy. A detailed analysis indicate that the sulfur is replaced by three water molecules, thereby changing the coordination number of Zn from four (as in the original peptide) to six (as in water).

  • 23.
    Brelsford, Craig C.
    et al.
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Morales, Luis Orlando
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Nezval, Jakub
    Faculty of Science, University of Ostrava, Ostrava, Czech Republic.
    Kotilainen, Titta K.
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Hartikainen, Saara M.
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Aphalo, Pedro J.
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Robson, Matthew
    Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Center (ViPS), Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
    Do UV‐A radiation and blue light during growth prime leaves to cope with acute high light in photoreceptor mutants of Arabidopsis thaliana?2019In: Physiologia Plantarum, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 165, no 3, p. 537-554Article in journal (Refereed)
    Abstract [en]

    We studied how plants acclimated to growing conditions that included combinations of blue light (BL) and ultraviolet (UV)‐A radiation, and whether their growing environment affected their photosynthetic capacity during and after a brief period of acute high light (as might happen during an under‐canopy sunfleck). Arabidopsis thaliana Landsberg erecta wild‐type were compared with mutants lacking functional blue light and UV photoreceptors: phototropin 1, cryptochromes (CRY1 and CRY2) and UV RESISTANT LOCUS 8 (uvr8). This was achieved using light‐emitting‐diode (LED) lamps in a controlled environment to create treatments with or without BL, in a split‐plot design with or without UV‐A radiation. We compared the accumulation of phenolic compounds under growth conditions and after exposure to 30 min of high light at the end of the experiment (46 days), and likewise measured the operational efficiency of photosystem II (ϕPSII, a proxy for photosynthetic performance) and dark‐adapted maximum quantum yield (Fv/Fm to assess PSII damage). Our results indicate that cryptochromes are the main photoreceptors regulating phenolic compound accumulation in response to BL and UV‐A radiation, and a lack of functional cryptochromes impairs photosynthetic performance under high light. Our findings also reveal a role for UVR8 in accumulating flavonoids in response to a low UV‐A dose. Interestingly, phototropin 1 partially mediated constitutive accumulation of phenolic compounds in the absence of BL. Low‐irradiance BL and UV‐A did not improve ϕPSII and Fv/Fm upon our acute high‐light treatment; however, CRYs played an important role in ameliorating high‐light stress.

  • 24. Brosché, Mikael
    et al.
    Gittins, John R.
    Sävenstrand, Helena
    Örebro University, Department of Natural Sciences.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Gene expression under environmental stresses: molecular marker analysis2002In: Molecular techniques in crop improvement / [ed] S. Mohan Jain, D.S. Brar, B.S. Ahloowalia, Boston: Kluwer Academic Publishers, 2002, p. 371-408Chapter in book (Other academic)
  • 25. Brosché, Mikael
    et al.
    Schuler, Mary A.
    Kalbina, Irina
    Örebro University, Department of Natural Sciences.
    Connor, Lynn
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Gene regulation by low level UV-B radiation: identification by DNA array analysis2002In: Photochemical and Photobiological Sciences, ISSN 1474-905X, E-ISSN 1474-9092, Vol. 1, no 9, p. 656-664Article in journal (Refereed)
    Abstract [en]

    UV-B radiation alters transcript levels of various defence genes and photosynthetic genes in plants. Utilising a DNA array with 5000 ESTs and cDNAs from Arabidopsis thaliana, 70 genes were found to show a greater than two-fold induction or repression of transcript levels. Six genes (MEB5.2, PyroA, Ubq3, Lhcb6, F5D21.10 and the gene for an RNA polymerase II subunit) were tested for stress specific gene regulation on northern blots with RNA from plants exposed to low dose UV-B radiation, ozone or wounding. Transcript levels for PyroA, Uhq3 and the gene for a RNA polymerase II subunit were all specifically increased by UV-B. MEB5.2 mRNA levels also rose, whereas Lhcb6 and FSD21.10 transcript levels decreased under all stresses. The PyroA gene product in fungi is needed for biosynthesis of pyridoxine, and might have a role in protection against singlet oxygen. The Ubq3 gene encodes the ubiquitin protein that is attached to proteins destined for degradation. MEB5.2 and F5D21.10 represent novel gene products whose function have not yet been identified. Pairwise comparisons between the UV-B inducible promoters have identified a series of elements present in the MEB5.2 and PyroA promoters, absent from promoters of genes for early phenylpropanoid metabolism and that may be responsible for modulating their UV-B responses.

  • 26.
    Béquignon, Olivier J. M.
    et al.
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Gómez-Tamayo, Jose C.
    Research Programme on Biomedical Informatics (GRIB), Department of Medicine and Life Sciences, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Carrer del Dr. Aiguader 88, 08002 Barcelona, Spain.
    Lenselink, Eelke B.
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Wink, Steven
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Hiemstra, Steven
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Lam, Chi Chung
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Gadaleta, Domenico
    Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS─Istituto di Ricerche Farmacologiche Mario Negri, Via la Masa 19, 20156 Milano, Italy.
    Roncaglioni, Alessandra
    Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS─Istituto di Ricerche Farmacologiche Mario Negri, Via la Masa 19, 20156 Milano, Italy.
    Norinder, Ulf
    Örebro University, School of Science and Technology.
    Water, Bob van de
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Pastor, Manuel
    Research Programme on Biomedical Informatics (GRIB), Department of Medicine and Life Sciences, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Carrer del Dr. Aiguader 88, 08002 Barcelona, Spain.
    van Westen, Gerard J. P.
    Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76, 2333 AL Leiden, The Netherlands.
    Collaborative SAR Modeling and Prospective In Vitro Validation of Oxidative Stress Activation in Human HepG2 Cells2023In: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 63, no 17, p. 5433-5445Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is the consequence of an abnormal increase of reactive oxygen species (ROS). ROS are generated mainly during the metabolism in both normal and pathological conditions as well as from exposure to xenobiotics. Xenobiotics can, on the one hand, disrupt molecular machinery involved in redox processes and, on the other hand, reduce the effectiveness of the antioxidant activity. Such dysregulation may lead to oxidative damage when combined with oxidative stress overpassing the cell capacity to detoxify ROS. In this work, a green fluorescent protein (GFP)-tagged nuclear factor erythroid 2-related factor 2 (NRF2)-regulated sulfiredoxin reporter (Srxn1-GFP) was used to measure the antioxidant response of HepG2 cells to a large series of drug and drug-like compounds (2230 compounds). These compounds were then classified as positive or negative depending on cellular response and distributed among different modeling groups to establish structure-activity relationship (SAR) models. A selection of models was used to prospectively predict oxidative stress induced by a new set of compounds subsequently experimentally tested to validate the model predictions. Altogether, this exercise exemplifies the different challenges of developing SAR models of a phenotypic cellular readout, model combination, chemical space selection, and results interpretation.

  • 27.
    Castro Alves, Victor
    et al.
    Department of Food Science and Experimental Nutrition, University of São Paulo, São Paulo, Brazil.
    Gomes, Daniel
    Sao Paulo Agency for Agribusiness Technology (APTA), Monte Alegre do Sul, Brazil.
    Menolli Jr., Nelson
    Department of Science and Mathematics, Science and Technology of São Paulo (IFSP), São Paulo, Brazil; Nucleus of Research in Mycology, Botanical Institute, São Paulo, Brazil.
    Sforça, Maurício L.
    Department of Food Science and Experimental Nutrition, University of São Paulo, São Paulo, Brazil; Laboratory of Nuclear Magnetic Resonance, Brazilian Center for Researchin Energy and Materials (CNPEM), Campinas, Brazil.
    Oliveira do Nascimento, João R.
    Department of Food Science and Experimental Nutrition, University of São Paulo, São Paulo, Brazil; Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, Brazil; Food Research Center (FoRC), CEPID-FAPESP, São Paulo, Brazil.
    Characterization and immunomodulatory effects of glucans from Pleurotus albidus, a promising species of mushroom for farming and biomass production2017In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 95, p. 215-223Article in journal (Refereed)
    Abstract [en]

    Polysaccharides from a number of mushroom species are recognized as functional food ingredients with potential health benefits, including immunomodulatory effects. In this study, polysaccharides extracted from the basidiome with cold water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo-(MyEX) and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a promising species for farming and biomass production, were analyzed for their chemical composition and structure and immunomodulatory effects on macrophages. Compositional (HPAEC-PAD and HPSEC-RID/MWD) and structural (FT-IR, 1D- and 2D-NMR) analyses identified BaCW and MyEX as beta-(1,6)-branched beta-(1,3)-glucans, BaHW and MyEN as alpha-(1,3)-(1,2)-branched alpha-(1,6)-glucans, and BaHA as a mixture of alpha-(1,6) and beta-(1,3)-glucans. BaCW and MyEX stimulated the production of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO), but not interleukin-6 (IL-6), and decreased phagocytosis of zymosan particles. In contrast, BaHW and MyEN induced TNF-alpha, NO and IL-6 production, and increased zymosan phagocytosis, while BaHA displayed intermediary effects in comparison the other polysaccharides. In conclusion, the basidiome and the submerged culture of P. albidus are sources of easily extractable alpha- and beta-glucans with potential immunomodulatory effects.

  • 28.
    Castro Alves, Victor
    et al.
    Örebro University, School of Science and Technology.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Öström, Åsa
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Strid, Åke
    Örebro University, School of Science and Technology.
    The taste of UV light: Using sensomics to improve horticultural quality2020In: UV4Plants Bulletin, ISSN 2343-323X, no 1, p. 5p. 39-43Article in journal (Refereed)
    Abstract [en]

    Greenhouse horticulture is in its broad definition the production of plant products within, under or sheltered by structures that provide protection against biotic and/or abiotic stress. In greenhouses, horticultural crops can grow protected from infectious agents and adverse weather conditions, allowing off-season, year-round production. However, greenhouse production often comes with a trade-off, which is a skewed light environment with a lack of UV light. 

    In some instances, the blockage of UV by greenhouse glass and plastic covers is beneficial from a commercial perspective, especially on tropical latitudes where plants can often encounter higher UV levels, which may impair plant growth and nutrient absorption (Krause et al. 1999; Verdaguer et al. 2017). On the other hand, reduced UV inside greenhouses may reduce the synthesis of metabolites associated with crop protection against biotic and abiotic stress, such as flavonoids, terpenoids and alkaloids (Yang et al. 2018). This reduction in the amount of protective compounds may not be seen as an important limitation in a protected environment, but these metabolic changes caused by reduced UV exposure may in fact negatively impact on product quality. For example, it is possible to improve of the aroma and taste of greenhouse tomato by exposing plants to low levels of supplementary UV light (Dzakovich et al. 2016).

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    The taste of UVlight: using sensomics to improve horticultural quality
  • 29.
    Cederfelt, Daniela
    et al.
    Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
    Badgujar, Dilip
    Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden; Department of Cell and Molecular Biology, Uppsala University, 751 23 Uppsala, Sweden.
    Au Musse, Ayan
    Örebro University, School of Science and Technology. Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
    Lohkamp, Bernhard
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Danielson, U. Helena
    Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
    Dobritzsch, Doreen
    Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
    The Allosteric Regulation of Β-Ureidopropionase Depends on Fine-Tuned Stability of Active-Site Loops and Subunit Interfaces2023In: Biomolecules, E-ISSN 2218-273X, Vol. 13, no 12, article id 1763Article in journal (Refereed)
    Abstract [en]

    The activity of β-ureidopropionase, which catalyses the last step in the degradation of uracil, thymine, and analogous antimetabolites, is cooperatively regulated by the substrate and product of the reaction. This involves shifts in the equilibrium of the oligomeric states of the enzyme, but how these are achieved and result in changes in enzyme catalytic competence has yet to be determined. Here, the regulation of human β-ureidopropionase was further explored via site-directed mutagenesis, inhibition studies, and cryo-electron microscopy. The active-site residue E207, as well as H173 and H307 located at the dimer-dimer interface, are shown to play crucial roles in enzyme activation. Dimer association to larger assemblies requires closure of active-site loops, which positions the catalytically crucial E207 stably in the active site. H173 and H307 likely respond to ligand-induced changes in their environment with changes in their protonation states, which fine-tunes the active-site loop stability and the strength of dimer-dimer interfaces and explains the previously observed pH influence on the oligomer equilibrium. The correlation between substrate analogue structure and effect on enzyme assembly suggests that the ability to favourably interact with F205 may distinguish activators from inhibitors. The cryo-EM structure of human β-ureidopropionase assembly obtained at low pH provides first insights into the architecture of its activated state. and validates our current model of the allosteric regulation mechanism. Closed entrance loop conformations and dimer-dimer interfaces are highly conserved between human and fruit fly enzymes.

  • 30.
    Chaillou, Thomas
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity2016In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 12, p. 3929-3941Article, review/survey (Refereed)
    Abstract [en]

    Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

  • 31. Cheng, J
    et al.
    Johansson, Magnus
    Nordlund, S
    Expression of P(II) and glutamine synthetase is regulated by P(II), the ntrBC products, and processing of the glnBA mRNA in Rhodospirillum rubrum1999In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 181, no 20, p. 6530-6534Article in journal (Refereed)
    Abstract [en]

    We have studied the transcription of the glnB and glnA genes in Rhodospirillum rubrum with firefly luciferase as a reporter enzyme. Under NH(4)(+) and N(2) conditions, glnBA was cotranscribed from a weak and a strong promoter. In nitrogen-fixing cultures, activity of the latter was highly enhanced by NtrC, but transcription from both promoters occurred under both conditions. There is no promoter controlling transcription of glnA alone, supporting our proposal that the glnA mRNA is produced by processing.

  • 32.
    Chondrogianni, Niki
    et al.
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Sakellari, Marianthi
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Lefaki, Maria
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Papaevgeniou, Nikoletta
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Gonos, Efstathios S.
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Proteasome activation delays aging in vitro and in vivo2014In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 71, p. 303-320Article, review/survey (Refereed)
    Abstract [en]

    Aging is a natural biological process that is characterized by a progressive accumulation of macromolecular damage. In the proteome, aging is accompanied by decreased protein homeostasis and function of the major cellular proteolytic systems, leading to the accumulation of unfolded, misfolded, or aggregated proteins. In particular, the proteasome is responsible for the removal of normal as well as damaged or misfolded proteins. Extensive work during the past several years has clearly demonstrated that proteasome activation by either genetic means or use of compounds significantly retards aging. Importantly, this represents a common feature across evolution, thereby suggesting proteasome activation to be an evolutionarily conserved mechanism of aging and longevity regulation. This review article reports on the means of function of these proteasome activators and how they regulate aging in various species. (C) 2014 Elsevier Inc. All rights reserved.

  • 33.
    Chow, Wah Soon
    et al.
    Research School of Biology, The Australian National University, Canberra ACT, Australia.
    Larkum, Antony W. D.
    Climate Change Cluster, University of Technology Sydney, Broadway NSW, Australia.
    Pfündel, Erhard
    Heinz Walz GmbH, Effeltrich, Germany.
    Ritchie, Raymond J.
    Faculty of Technology & Environment, Prince of Songkla University, Phuket Campus, Kathu, Phuket, Thailand.
    Scheer, Hugo
    Department Biologie 1 – Botanik, Ludwig-Maximilians-Universität, Munich, Germany.
    Strid, Åke
    Örebro University, School of Science and Technology.
    A tribute to Robert John Porra (august 7, 1931–may 16, 2019)2021In: Photosynthesis Research, ISSN 0166-8595, E-ISSN 1573-5079, Vol. 147, no 2, p. 125-130Article in journal (Refereed)
    Abstract [en]

    Robert John Porra (7.8.1931–16.5.2019) is probably best known for his substantial practical contributions to plant physiology and photosynthesis by addressing the problems of both the accurate spectroscopic estimation and the extractability of chlorophylls in many organisms. Physiological data and global productivity estimates, in particular of marine primary productivity, are often quoted on a chlorophyll basis. He also made his impact by work on all stages of tetrapyrrole biosynthesis: he proved the C5 pathway to chlorophylls, detected an alternative route to protoporphyrin in anaerobes and the different origin of the oxygen atoms in anaerobes and aerobes. A brief review of his work is supplemented by personal memories of the authors.

  • 34.
    Czégény, Gyula
    et al.
    Department of Plant Biology, University of Pécs, Pécs, Hungary.
    Körösi, Laszlo
    Research institute for Viticulture and Oenology, University of Pécs, Pécs, Hungary.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Hideg, Éva
    Department of Plant Biology, University of Pécs, Pécs, Hungary.
    Multiple roles for Vitamin B6in plant acclimation to UV-B2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, no 1, article id 1259Article in journal (Refereed)
    Abstract [en]

    Direct and indirect roles of vitamin B6in leaf acclimation to supplementary UV-B radiation are shown in vitamin B6deficient Arabidopsis thalianamutant rsr4-1 and C24 wild type. Responses to 4 days of 3.9 kJ m-2d-1 biologically effective UV-B dose were compared in terms of leaf photochemistry, vitamer content, and antioxidant enzyme activities; complemented with a comprehensive study of vitamer ROS scavenging capacities. Under UV-B, rsr4-1 leaves lost more (34%) photochemical yield than C24 plants (24%). In the absence of UV-B, rsr4-1 leaves contained markedly less pyridoxal-5’-phosphate (PLP) than C24 ones, but levels increased up to the C24 contents in response to UV-B. Activities of class-III ascorbate and glutathione peroxidases increased in C24 leaves upon the UV-B treatment but not in the rsr4-1 mutant. SOD activities remained the same in C24 but decreased by more than 50% in rsr4-1 under UV-B. Although PLP was shown to be an excellent antioxidant in vitro, our results suggest that the UV-B protective role of B6 vitamers is realized indirectly, via supporting peroxidase defence rather than by direct ROS scavenging. We hypothesize that the two defence pathways are linked through the PLP-dependent biosynthesis of cystein and heme, affecting peroxidases.

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    Multiple roles for Vitamin B6 in plant acclimation to UV-B
  • 35.
    Czégény, Gyula
    et al.
    Institute of Biology, University of Pécs, Pécs, Hungary; Institute of Plant Biology, Biological Research Centre, Szeged, Hungary.
    Wu, Min
    Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
    Dér, András
    Institute of Biophysics, Biological Research Centre, Szeged, Hungary.
    Eriksson, Leif A
    Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Hideg, Éva
    Institute of Biology, University of Pécs, Pécs, Hungary.
    Hydrogen peroxide contributes to the ultraviolet-B (280-315 nm) induced oxidative stress of plant leaves through multiple pathways2014In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 588, no 14, p. 2255-2261Article in journal (Refereed)
    Abstract [en]

    Solar UV-B (280-315 nm) radiation is a developmental signal in plants but may also cause oxidative stress when combined with other environmental factors. Using computer modelling and in solution experiments we show that UV-B is capable of photosensitizing hydroxyl radical production from hydrogen peroxide. We present evidence that the oxidative effect of UV-B in leaves is at least two-fold: (i) it increases cellular hydrogen peroxide concentrations, to a larger extent in pyridoxine antioxidant mutant pdx1.3-1 Arabidopsis and (ii) is capable of a partial photo-conversion of both ‘natural’ and ‘extra’ hydrogen peroxide to hydroxyl radicals. As stress conditions other than UV can increase cellular hydrogen peroxide levels, synergistic deleterious effects of various stresses may be expected already under ambient solar UV-B.

  • 36.
    Danielsson Tham, Marie-Louise
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Loncarevic, Semir
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Serovars and genomic characteristics of Listeria monocytogenes isolated from raw milk cheese1996Conference paper (Other academic)
  • 37.
    Day, Michaela J.
    et al.
    National Infection Service, Public Health England, London, UK.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhea and other STIs.
    Woodford, Neil
    National Infection Service, Public Health England, London, UK.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Cole, Michelle J.
    National Infection Service, Public Health England, London, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhea and other STIs.
    Euro-GASP, network
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 20162018In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 18, no 1, article id 609Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2016 (25 countries), linked to patient epidemiological data, and compared with data from previous years.

    METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests.

    RESULTS: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years.

    CONCLUSIONS: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

  • 38.
    Dinoto, Achmad
    et al.
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido .
    Marques, Tatiana M.
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Sakamoto, Kanta
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Fukiya, Satoru
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Watanabe, Jun
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Ito, Susumu
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Yokota, Atsushi
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Population dynamics of Bifidobacterium species in human feces during raffinose administration monitored by fluorescence in situ hybridization-flow cytometry2006In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 72, no 12, p. 7739-47Article in journal (Refereed)
    Abstract [en]

    The population dynamics of bifidobacteria in human feces during raffinose administration were investigated at the species level by using fluorescence in situ hybridization (FISH) coupled with flow cytometry (FCM) analysis. Although double-staining FISH-FCM using both fluorescein isothiocyanate (FITC) and indodicarbocyanine (Cy5) as labeling dyes for fecal samples has been reported, the analysis was interfered with by strong autofluorescence at the FITC fluorescence region because of the presence of autofluorescence particles/debris in the fecal samples. We circumvented this problem by using only Cy5 fluorescent dye in the FISH-FCM analysis. Thirteen subjects received 2 g of raffinose twice a day for 4 weeks. Fecal samples were collected, and the bifidobacterial populations were monitored using the established FISH-FCM method. The results showed an increase in bifidobacteria from about 12.5% of total bacteria in the prefeeding period to about 28.7 and 37.2% after the 2-week and 4-week feeding periods, respectively. Bifidobacterium adolescentis, the Bifidobacterium catenulatum group, and Bifidobacterium longum were the major species, in that order, at the prefeeding period, and these bacteria were found to increase nearly in parallel during the raffinose administration. During the feeding periods, indigenous bifidobacterial populations became more diverse, such that minor species in human adults, such as Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium dentium, and Bifidobacterium angulatum, proliferated. Four weeks after raffinose administration was stopped, the proportion of each major bifidobacterial species, as well as that of total bifidobacteria, returned to approximately the original values for the prefeeding period, whereas that of each minor species appeared to differ considerably from its original value. To the best of our knowledge, these results provide the first clear demonstration of the population dynamics of indigenous bifidobacteria at the species level in response to raffinose administration.

  • 39.
    Duszka, Kalina
    et al.
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Center for Integrative Genomics, University of Lausanne, Génopode, Lausanne, Switzerland; Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
    Oresic, Matej
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University,Turku, Finland.
    Le May, Cedric
    Institut du Thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
    König, Jürgen
    Department of Nutritional Sciences, University of Vienna, Vienna, Austria; Vienna Metabolomics Center (VIME), University of Vienna, Vienna, Austria.
    Wahli, Walter
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Center for Integrative Genomics, University of Lausanne Génopode, Lausanne, Switzerland; ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), Toulouse, France.
    PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium2017In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 18, no 12, article id E2559Article in journal (Refereed)
    Abstract [en]

    Nuclear receptor PPARγ affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPARγ knockout mice (iePPARγKO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPARγKO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium. Gavage with the medium chain saturated FA-rich coconut oil did not result in differences between the two genotypes. Furthermore, the iePPARγKO mice did not exhibit defective lipid uptake and stomach emptying; however, their intestinal transit was more rapid than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPARγKO mice had higher body lean mass than the WT mice. We conclude that intestinal epithelium PPARγ is activated preferentially by long chain unsaturated FAs compared to medium chain saturated FAs. Furthermore, we hypothesize that the iePPARγKO phenotype originates from altered lipid metabolism and release in epithelial cells, as well as changes in intestinal motility.

  • 40.
    Dzialanski, Zbigniew
    et al.
    University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Barany, Michael
    Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden; School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Engfeldt, Peter
    Örebro University, School of Medical Sciences. University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Olsson, Lovisa A.
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Faculty of Medicine and Health, Umeå University, Umeå, Sweden.
    Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 3, p. 248-252Article in journal (Refereed)
    Abstract [en]

    Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist.

    Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test.

    Methods: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274).

    Results: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups.

    Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.

  • 41.
    Díaz-Ramos, L. Aranzazú
    et al.
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    O'Hara, Andrew
    Örebro University, School of Science and Technology. Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    Kanagarajan, Selvaraju
    Department of Plant Breeding, Swedish University of Agricultural Sciences, Alnarp, Sweden; School of Science & Technology, Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Farkas, Daniel
    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Jenkins, Gareth I
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    Difference in the action spectra for UVR8 monomerisation and HY5 transcript accumulation in Arabidopsis2018In: Photochemical and Photobiological Sciences, ISSN 1474-905X, E-ISSN 1474-9092, Vol. 17, no 8, p. 1108-1117Article in journal (Refereed)
    Abstract [en]

    The photoreceptor UV RESISTANCE LOCUS 8 (UVR8) activates photomorphogenic responses when plants are exposed to ultraviolet-B (UVB) light. However, whereas the absorption spectrum of UVR8 peaks at 280 nm, action spectra for several photomorphogenic UV-B responses show maximal photon effectiveness at 290-300 nm. To investigate this apparent discrepancy we measured the effectiveness of UV wavelengths in initiating two responses in Arabidopsis: photoconversion of homodimeric UVR8 into the monomeric form, which is active in signaling, and accumulation of transcripts of the ELONGATED HYPOCOTYL 5 (HY5) transcription factor, which has a key role in UVR8-mediated responses. When purified UVR8 or Arabidopsis leaf extracts were exposed to UV light monomerisation was maximal at approximately 280 nm, which correlates with the UVR8 absorption spectrum. When intact plants were exposed to UV, monomerisation was most strongly initiated at approximately 290 nm, and this shift in maximal effectiveness could be explained by strong absorption or reflectance at 280 nm by leaf tissue. Notably, the action spectrum for accumulation of HY5 transcripts in the same leaf tissue samples used to assay UVR8 dimer/monomer status peaked at approximately 300 nm. Possible reasons for the difference in maximal photon effectiveness of UVR8 monomerisation and HY5 transcript accumulation in leaf tissue are discussed.

  • 42.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Lathrop Stern, Lori
    Labus, Jennifer
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Evaluating the effects of probiotic intake on brain activity during an emotional attention task and blood markers related to stress in healthy subjects2019Conference paper (Refereed)
  • 43.
    Eriksson, Leif A.
    et al.
    Göteborgs universitet, Göteborg.
    Sirsjö, Allan
    Örebro University, School of Medical Sciences.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Tetrazole derivatives as cytochrome p450 inhibitors2019Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    According to the invention there is provided a compound of formula I, wherein Rand Rhave meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases.

    Download full text (pdf)
    Patent
  • 44.
    Fallet, Manon
    Örebro University, School of Science and Technology.
    Epigenetic Inheritance2024In: Epigenetics in Biological Communication / [ed] Guenther Witzany, Springer, 2024, p. 87-130Chapter in book (Other academic)
    Abstract [en]

    The field of epigenetics, orchestrating molecular communication at the genome-phenotype interface, has gained significant importance over the last decades. Mitotic inheritance, ensuring the propagation of epigenetic information throughout cell division, is crucial for preserving cell fate, functionality, organisms’ development, and for transcriptional memory of past events. In addition, the more elusive meiotic inheritance, responsible for transmitting epigenetic information across generations, may contribute to intergenerational or transgenerational disorders or empower offspring with the ability to prosper under specific environmental contexts. This book chapter provides an in-depth description of the intricate mechanisms governing epigenetic information transmission during both mitosis and meiosis, with illustrative examples. Furthermore, the chapter investigates the role of epigenetic inheritance in environmental studies, addressing current challenges and offering perspectives for future research in this dynamic field.

  • 45.
    Fang, Wei
    et al.
    Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, Hubei, PR China.
    Santosh, Lamichhane
    Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, Hubei, PR China; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Lipidomes in health and disease: Analytical strategies and considerations2019In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 120, article id 115664Article, review/survey (Refereed)
    Abstract [en]

    Lipidomics is a rapidly-growing field which focuses on global characterization of lipids at molecular and systems levels. As small changes in the concentrations of lipids may have important physiological consequences, much attention in the field has recently been paid to more accurate quantitation and identification of lipids. Community-wide efforts have been initiated, aiming to develop best practices for lipidomic analyses and reporting of lipidomic data. Nevertheless, current approaches for comprehensive analysis of lipidomes have some inherent challenges and limitations. Additionally, there is, currently, limited knowledge concerning the impacts of various external and internal exposures on lipid levels. In this review, we discuss the recent progress in lipidomics analysis, with a primary focus on analytical approaches, as well as on the different sources of variation in quantifying lipid levels, both technical and biological.

    Download full text (pdf)
    Lipidomes in health and disease: Analytical strategies and considerations
  • 46.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Liang, Chun
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Li, Mei
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Fall, Katja
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Aaseth, Jan
    Faculty of Public Health, Hedmark University College, Elverum, Norway; Kongsvinger Hospital Division, Innlandet Hospital Trust, Kongsvinger, Norway.
    Cao, Yang
    Örebro University, School of Medical Sciences. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies2016In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, p. 64-73Article, review/survey (Refereed)
    Abstract [en]

    Background: Although epidemiology studies have reported the relationship, including a dose-response relationship, between dietary magnesium intake and risk of cardiovascular disease (CVD), the risk for CVD mortality is inconclusive and the evidence for a dose-response relationship has not been summarized.

    Objective: We conducted a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the association of dietary magnesium intake with risk of CVD mortality and describe their dose-response relationship.

    Design: We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to August 2015, and reviewed references lists of retrieved articles. We included population-based studies that reported mortality risks, i.e. relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs) of CVD mortality or cause-specific CVD death. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines.

    Results: Out of 3002 articles, 9 articles from 8 independent studies met the eligibility criteria. These studies comprised 449,748 individuals and 10,313 CVD deaths. Compared with the lowest dietary magnesium consumption group in the population, the risk of CVD mortality was reduced by 16% in women and 8% in men. No significant linear dose-response relationship was found between increment in dietary magnesium intake and CVD mortality across all the studies. After adjusting for age and BMI, the risk of CVD mortality was reduced by 24-25% per 100 mg/d increment in dietary magnesium intake in women of all the participants and in all the US participants.

    Conclusion: Although the combined data confirm the role of dietary magnesium intake in reducing CVD mortality, the dose-response relationship was only found among women and in US population.

  • 47.
    Farkas, Sanja
    Örebro University, School of Science and Technology. Örebro University.
    Development of a UV-B marker in plants2009Licentiate thesis, monograph (Other academic)
  • 48.
    Filonova, Lada
    et al.
    WURC, Department of Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Gunnarsson, Lavinia Cicortas
    Örebro University. Department of Immunotechnology, Lund University, Lund, Sweden; Affitech AS, Oslo, Norway.
    Daniel, Geoffrey
    WURC, Department of Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Synthetic xylan-binding modules for mapping of pulp fibres and wood sections2007In: BMC Plant Biology, E-ISSN 1471-2229, Vol. 7, article id 54Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The complex carbohydrate composition of natural and refined plant material is not known in detail but a matter that is of both basic and applied importance. Qualitative assessment of complex samples like plant and wood tissues requires the availability of a range of specific probes. Monoclonal antibodies and naturally existing carbohydrate binding modules (CBMs) have been used in the past to assess the presence of certain carbohydrates in plant tissues. However, the number of natural CBMs is limited and development of carbohydrate-specific antibodies is not always straightforward. We envisage the use of sets of very similar proteins specific for defined targets, like those developed by molecular evolution of a single CBM scaffold, as a suitable strategy to assess carbohydrate composition. An advantage of using synthetic CBMs lies in the possibility to study fine details of carbohydrate composition within non-uniform substrates like plant cell walls as made possible through minor differences in CBM specificity of the variety of binders that can be developed by genetic engineering.

    RESULTS: A panel of synthetic xylan-binding CBMs, previously selected from a molecular library based on the scaffold of CBM4-2 from xylanase Xyn10A of Rhodothermus marinus, was used in this study. The wild type CBM4-2 and evolved modules both showed binding to wood sections. However, differences were observed in the staining patterns suggesting that these modules have different xylan-binding properties. Also the staining stability varied between the CBMs, the most stable staining being obtained with one (X-2) of the synthetic modules. Treatment of wood materials resulted in altered signal intensities, thereby also demonstrating the potential application of engineered CBMs as analytical tools for quality assessment of diverse plant material processes.

    CONCLUSION: In this study we have demonstrated the usefulness of synthetic xylan-binding modules as specific probes in analysis of hemicelluloses (xylan) in wood and fibre materials.

  • 49.
    Finckenberg, Piet
    et al.
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Eriksson, Ove
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Baumann, Marc
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Merasto, Saara
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Lalowski, Maciej M.
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Levijoki, Jouko
    Orion Pharma Ltd, Espoo, Finland.
    Haasio, Kristiina
    Orion Pharma Ltd, Espoo, Finland.
    Kytö, Ville
    Department of Medicine, Turku University Hospital, Turku, Finland.
    Muller, Dominik N.
    Experimental and Clinical Research Center, Max Delbrück Center, Berlin, Germany.
    Luft, Friedrich C.
    Experimental and Clinical Research Center, Max Delbrück Center, Berlin, Germany.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Mervaala, Eero
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy2012In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 59, no 1, p. 76-84Article in journal (Refereed)
    Abstract [en]

    Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications.

  • 50.
    Fornander, Louise
    Institutionen för klinisk och experimentell medicin, Linköpings universitet, Linköping, Sweden.
    Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid.

    This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using twodimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health.

    Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified.

    Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation.

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