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  • 1.
    Aarseth Larsson, Kim
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Inhibition of SIRT1 Alters Apoptotic and Sex Related Genes in Zebrafish (Danio rerio)2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide - dependent deacetylase that belongs to the sirtuin protein family. The protein has been linked to both cancer through its effect on p53 and age related illnesses through its effect on peroxisome proliferator-activated receptor gamma (PPAR-γ). Recent data have shown a correlation between SIRT1, male fertility and spermatogenesis. Because the mechanism of sex differentiation in zebrafish is still not wellunderstood the sirt1 gene is an attractive target to study in order to improve our understanding of this topic. Zebrafish of different age were exposed to various concentrations of EX-527 toinhibit the SIRT1 protein. This was followed by qRT-PCR analysis of apoptotic and sex-related genes. Both apoptotic and sex-related gene expression levels were affected by the exposure. There were differences in genes that were affected, both between the concentrations of EX-527, and between the ages of the exposed zebrafish. The male- specific gene sexdetermining region Y box 9A (sox9a) was down-regulated at both studied EX-527 concentrations in both zebrafish larvae and juveniles. The exposure of the EX-527 resulted in no significant difference in sex-ratio. Further studies are required to describe the pathway for SIRT1 gene regulation in zebrafish.

  • 2.
    Abderhim, Walid Tajeddinn
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Morphological Analysis of β-catenin and E-cadherin in Colorectal Cancer2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 3.
    Abuabaid, Hanan
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Karlsson, Mattias
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Scherbak, Nikolai
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Jass, Jana
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Probiotic Lactobacillus rhamnosus alters inflammatory responses of bladder epithelial and macrophage-like cells in co-cultureManuskript (preprint) (Annet vitenskapelig)
  • 4.
    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 patients1995Inngår i: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 19, nr 4, s. 272-278Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5.
    Ahmad, Abrar
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Kras and Braf mutation analysis in colon cancer by pyrosequencing2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 6.
    Alfaro-Moreno, Ernesto
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Quintana-Belmares, R.
    Instituto Nacional de Cancerologia, Investigacion Basica, Mexico City, Mexico.
    Montiel-Davalos, A.
    Instituto Nacional de Cancerologia, Investigacion Basica, Mexico City, Mexico.
    Gustafsson, A.
    Örebro University, Man-Technology-Environment Research Center, Örebro, Sweden.
    Miranda, J.
    Universidad Nacional Autonoma de Mexico, Instituto de Fisica, Mexico City, Mexico.
    Lopez-Marure, R.
    Instituto Nacional de Cardiologia, Investigacion, Mexico City, Mexico.
    Rosas-Perez, I.
    Universidad Nacional Autonoma de Mexico, Centro de Ciencias de la Atmosfera, Mexico City, Mexico.
    Expression of receptors for adhesion molecules in monocytes exposed to urban particulate matter is independent of size and composition of the particles2019Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 314, nr Suppl., s. S232-S233Artikkel i tidsskrift (Annet vitenskapelig)
  • 7.
    Alfonso, Sébastien
    et al.
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France; UMR MARBEC, Ifremer, IRD, UM2, CNRS, Laboratoire Adaptation et Adaptabilités des Animaux et des Systèmes, Route de Maguelone, F-34250, Palavas-les-Flots, France.
    Blanc, Mélanie
    Örebro universitet, Institutionen för naturvetenskap och teknik. Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Joassard, Lucette
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Keiter, Steffen
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Munschy, Catherine
    Ifremer, Laboratoire Biogéochimie des Contaminants Organiques, Rue de l'Ile d'Yeu, BP 21105, F-44311, Nantes, Cedex 3, France.
    Loizeau, Véronique
    Ifremer, Laboratoire Biogéochimie des Contaminants Organiques, ZI Pointe du Diable, CS 10070, F-29280, Plouzané, France.
    Bégout, Marie-Laure
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Cousin, Xavier
    UMR MARBEC, Ifremer, IRD, UM2, CNRS, Laboratoire Adaptation et Adaptabilités des Animaux et des Systèmes, Route de Maguelone, F-34250, Palavas-les-Flots, France; Inra, UMR GABI, Inra, AgroParisTech, Domaine de Vilvert, Batiment 231, F-78350 Jouy-en-Josas, France.
    Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture2019Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 208, s. 29-38Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants extensively used during the 20th century and still present in aquatic environments despite their ban. Effects of exposure to these compounds over generations are poorly documented. Therefore, our aims were to characterize behavioral responses and underlying molecular mechanisms in zebrafish exposed to an environmentally relevant mixture of PCBs and PBDEs as well as in four unexposed offspring generations. Zebrafish (F0) were chronically exposed from the first meal onward to a diet spiked with a mixture containing 22 PCB and 7 PBDE congeners in proportions and concentrations reflecting environmental situations (ΣPCBs = 1991 and ΣPBDEs = 411 ng/g). Four offspring generations (F1 to F4) were obtained from this F0 and were not further exposed. Behavior was assessed at both larval and adult stages. Mechanisms related to behavioral defects (habenula maturation and c-fos transcription) and methylation (dnmts transcription) were monitored in larvae. Exposed adult F0 as well as F1 and F3 adults displayed no behavioral change while F2 expressed anxiety-like behavior. Larval behavior was also disrupted, i.e. hyperactive after light to dark transition in F1 or hypoactive in F2, F3 and F4. Behavioral disruptions may be related to defect in habenula maturation (observed in F1) and change in c-fos transcription (observed in F1 and F2). Transcription of the gene encoding DNA methyltransferase (dnmt3ba) was also modified in all generations. Our results lead us to hypothesize that chronic dietary exposure to an environmentally relevant mixture of PCB and PBDE triggers multigenerational and transgenerational molecular and behavioral disruptions in a vertebrate model.

  • 8.
    Andersson, Anneli
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Tuvblad, Catherine
    Örebro universitet, Institutionen för juridik, psykologi och socialt arbete. University of Southern California, Department of Psychology, Los Angeles CA, USA.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Chen, Qi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Larsson, Henrik
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Genetic overlap between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms: a systematic review and meta-analysis2018Inngår i: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 48, nr 6, s. 455-456Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder (Wilens, Biederman & Spencer 2002) and affects approximately 5% of children (Polanczyk, de Lima, Horta, Biederman & Rohde 2007). About half of those diagnosed in childhood continue to have the diagnosis and symptoms in adulthood (Kessler et al. 2006). The co-occurrence of ADHD with other psychiatric disorder symptoms (Burt et al. 2001; Cole et al. 2009; Polderman et al. 2014) has been suggested to be partly explained by a shared genetic vulnerability (Polderman et al. 2014). However, the strength of the genetic overlap is currently unclear. Also, no study has examined whether the genetic correlations differs between age groups (childhood versus adulthood), by rater (self-report, other informant, combined (parent-teacher, parent-twin, teacher-twin)), or by type of psychiatric disorder symptoms (externalizing, internalizing, neu-rodevelopmental). To address this gap, we conducted a systematic literature search to identify relevant twin studies, in PubMed, PsycINFO, and EMBASE. A total of 31 articles were identified and included in the present study. The pooled estimates showed that the comorbidity between ADHD and diverse psychiatric disorder symptoms were explained by shared genetic effectsrg= 0.50 (0.43–0.56). A similar shared genetic overlap between ADHD and psychiatric disorder symptoms was observed in both childhood rg= 0.51(0.42–0.61) and adulthood rg= 0.47 (0.40–0.53). Similar results werealso found for self-reports rg= 0.49 (0.42–0.55), other informants rg= 0.50 (0.40–0.60), and combined raters rg= 0.51 (0.30–0.69). Further, the strength of the genetic correlations of ADHD with the externalizing rg= 0.49 (0.39–0.59), internalizing rg= 0.55 (0.40–0.68) and neurodevelopmental rg= 0.47 (0.40–0.53) spectrums were similar in magnitude. These findings emphasize the presence of a shared genetic liability between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms, independent of age and rater.

    References

    Burt, S. A., Krueger, R. F., McGue, M., Iacono, W. G. (2001).Sources of covariation among attention-deficit/hyperactivity disorder,oppositional defiant disorder, and conduct disorder: the importance ofshared environment.Journal of Abnormal Psychology, 4, 516–525.

    Cole, J., Ball, H. A., Martin, N. C., Scourfield, J., McGuffin, P.(2009). Genetic overlap between measures of hyperactivity/inatten-tion and mood in children and adolescents.J Am Acad Child AdolescPsychiatry48, 1094–1101.

    Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C.K., Demler, O., Faraone, S. V., Greenhill, L. L., Howes, M. J., Secnik,K., Spencer, T., Ustun, T. B., Walters, E. E., Zaslavsky, A. M. (2006).The prevalence and correlates of adult ADHD in the United States:results from the National Comorbidity Survey Replication.Am JPsychiatry, 163, 716–723.

    Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., Rohde,L. A. (2007). The worldwide prevalence of ADHD: a systematicreview and metaregression analysis.Am J Psychiatry, 164, 942-8.

    Polderman, T. J., Hoekstra, R. A., Posthuma, D., Larsson, H.(2014). The co-occurrence of autistic and ADHD dimensions inadults: an etiological study in 17,770 twins.Transl Psychiatry2014;4: e435.

    Wilens, T. E., Biederman, J., Spencer, T. J. (2002). Attentiondeficit/hyperactivity disorder across the lifespan.Annual Review Med53:113–131.

  • 9.
    Andersson, Henrik
    et al.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Andersson, Blanka
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Eklund, Daniel
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ngoh, Eyler
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Persson, Alexander
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Svensson, Kristoffer
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lerm, Maria
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Blomgran, Robert
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Stendahl, Olle
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, artikkel-id e101514Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.

  • 10.
    Andersson, Josefin
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Utvärdering av Malaria Antigen ELISA kit för diagnostik av malaria vid Christian Medical College and Hospital i Vellore, Indien.: en jämförande studie mellan Quantitative buffy coat och enzyme-linked immunosorbent assays (ELISA) metodik.2006Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Malaria är ett globalt hälsoproblem som orsakar många dödsfall runt om i världen varje år och nästan hälften av jordens befolkning ligger i riskzonen att drabbas av sjukdomen. I Indien drabbas mellan 2-3 miljoner människor varje år och det inträffar omkring 900 dödsfall. Malaria orsakas av Plasmodium sp. som är en protozoe, och det finns fyra olika arter som är patogena för människor, P. vivax, P. ovale, P. falciparium samt P. malariae.

    Vanliga metoder för att diagnostisera malaria är genom tunna och tjocka blodutstryk som färgas till exempel med Giemsa, Fields eller Leishmans färgningsteknik och studeras mikroskopiskt, Quantitative Buffy Coat (QBC), PCR tester, acridinorange färgning samt olika immunologiska tester för detektion av antikroppar eller antigen som till exempel enzyme-linked immunosorbent assays (ELISA) test och dipstick test.

    Syftet med denna studie är att utvärdera om en användning av SD Bio Line Malaria Antigen ELISA kit ger en mer känslig, tillförlitlig, praktisk samt mindre kostsam diagnostikmetod för malaria hos patienter med misstänkt malariainfektion än den nuvarande guldstandardmetoden, QBC tillsammans med blodutstryk, vid Christian Medical College and Hospital i Vellore.

    Patientproverna har i både ELISA testet samt QBC testet tillsammans med utstryk erhållit samma resultat vilket tyder på att SD Bio Line Malaria Antigen ELISA kitet skulle kunna vara en lika bra diagnostikmetod som QBC testet för diagnos av malaria. ELISA kitet har dock fler nackdelar, i jämförelse med QBC testet, så därför är slutsatsen att SD Bio Line Malaria Antigen ELISA kitet inte är en mer lämplig diagnostisk metod för malaria än den som används vid CMCH. Men då ELISA testet ändå ger en säker diagnos, enligt resultatet i studien, kan den vara ett lämpligt test inom något annat användningsområde.

  • 11. Andersson, P. L.
    et al.
    Berg, A. H.
    Bjerselius, R.
    Norrgren, L.
    Olsén, H.
    Olsson, Per-Erik
    Institutionen för Molekylärbiologi, Umeå Universitet.
    Örn, S.
    Tysklind, M.
    Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and arctic char after three different routes of exposure2001Inngår i: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341, E-ISSN 1432-0703, Vol. 40, nr 4, s. 519-530Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 12.
    Andersson, Sören
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    CHIMERIC MOMP ANTIGEN2015Patent (Annet (populærvitenskap, debatt, mm))
  • 13.
    Andersson, Sören
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Chimeric MOMP antigen2014Patent (Annet (populærvitenskap, debatt, mm))
    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.

  • 14. Andorf, Sandra
    et al.
    Altmann, T
    Witucka-Wall, H
    Selbig, Joachim
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems-biology approach to heterosis2009Konferansepaper (Fagfellevurdert)
  • 15.
    Andorf, Sandra
    et al.
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Gärtner, Tanja
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Steinfath, Matthias
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Witucka-Wall, Hanna
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Altmann, Thomas
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Towards systems biology of heterosis: a hypothesis about molecular network structure applied for the Arabidopsis metabolome2009Inngår i: EURASIP Journal on Bioinformatics and Systems Biology, ISSN 1687-4145, E-ISSN 1687-4153, artikkel-id 147157Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We propose a network structure-based model for heterosis, and investigate it relying on metabolite profiles from Arabidopsis. A simple feed-forward two-layer network model (the Steinbuch matrix) is used in our conceptual approach. It allows for directly relating structural network properties with biological function. Interpreting heterosis as increased adaptability, our model predicts that the biological networks involved show increasing connectivity of regulatory interactions. A detailed analysis of metabolite profile data reveals that the increasing-connectivity prediction is true for graphical Gaussian models in our data from early development. This mirrors properties of observed heterotic Arabidopsis phenotypes. Furthermore, the model predicts a limit for increasing hybrid vigor with increasing heterozygosity--a known phenomenon in the literature.

  • 16.
    Andorf, Sandra
    et al.
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Department of Medicine, Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
    Meyer, Rhonda C
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Selbig, Joachim
    Bioinformatics Chair, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
    Altmann, Thomas
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Repsilber, Dirk
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Integration of a systems biological network analysis and QTL results for biomass heterosis in Arabidopsis thaliana2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 11, artikkel-id e49951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To contribute to a further insight into heterosis we applied an integrative analysis to a systems biological network approach and a quantitative genetics analysis towards biomass heterosis in early Arabidopsis thaliana development. The study was performed on the parental accessions C24 and Col-0 and the reciprocal crosses. In an over-representation analysis it was tested if the overlap between the resulting gene lists of the two approaches is significantly larger than expected by chance. Top ranked genes in the results list of the systems biological analysis were significantly over-represented in the heterotic QTL candidate regions for either hybrid as well as regarding mid-parent and best-parent heterosis. This suggests that not only a few but rather several genes that influence biomass heterosis are located within each heterotic QTL region. Furthermore, the overlapping resulting genes of the two integrated approaches were particularly enriched in biomass related pathways. A chromosome-wise over-representation analysis gave rise to the hypothesis that chromosomes number 2 and 4 probably carry a majority of the genes involved in biomass heterosis in the early development of Arabidopsis thaliana.

  • 17. Andorf, Sandra
    et al.
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems biological approach to heterosis2009Inngår i: Neue Methoden der Biometrie: 55. Biometrisches Kolloquium / [ed] R. Foraita, T. Gerds, L. A. Hothorn, M. Kieser, O. Kuß, U. Munzel, R. Vonk, A. Ziegler, 2009Konferansepaper (Fagfellevurdert)
  • 18.
    Andorf, Sandra
    et al.
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
    Selbig, Joachim
    University of Potsdam, Potsdam-Golm, Germany.
    Altmann, T
    Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany.
    Witucka-Wall, H
    University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Gremany.
    Heterosis in Arabidopsis thaliana: A metabolite network structure approach2010Inngår i: 11th Day of the Doktoral Student: abstract; 19 May 2010, Dummerstorf, Dummerstorf, Germany: FBN , 2010, s. 7-10Konferansepaper (Fagfellevurdert)
  • 19.
    Andorf, Sandra
    et al.
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Selbig, Joachim
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Altmann, Thomas
    Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Poos, Kathrin
    University of Applied Sciences Gelsenkirchen Site Recklinghausen, Recklinghausen, Germany .
    Witucka-Wall, Hanna
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis2010Inngår i: Theoretical and Applied Genetics, ISSN 0040-5752, E-ISSN 1432-2242, Vol. 120, nr 2, s. 249-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heterosis is a well-known phenomenon but the underlying molecular mechanisms are not yet established. To contribute to the understanding of heterosis at the molecular level, we analyzed genome-wide gene expression profile data of Arabidopsis thaliana in a systems biological approach. We used partial correlations to estimate the global interaction structure of regulatory networks. Our hypothesis states that heterosis comes with an increased number of partial correlations which we interpret as increased numbers of regulatory interactions leading to enlarged adaptability of the hybrids. This hypothesis is true for mid-parent heterosis for our dataset of gene expression in two homozygous parental lines and their reciprocal crosses. For the case of best-parent heterosis just one hybrid is significant regarding our hypothesis based on a resampling analysis. Summarizing, both metabolome and gene expression level of our illustrative dataset support our proposal of a systems biological approach towards a molecular basis of heterosis.

  • 20. Andorf, Sandra
    et al.
    Selbig, Joachim
    Meyer, Rhonda
    Altmann, Thomas
    Repsilber, Dirk
    Integrating a molecular network hypothesis and QTL results for heterosis in Arabidopsis thaliana2010Inngår i: Statistical Computings 2010: Abstracts der 42. Arbeitstagung, 2010, Vol. 5Konferansepaper (Fagfellevurdert)
  • 21.
    Andraos, R.
    et al.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Södergren, A.L.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Öllinger, K.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Reactive oxygen species enhance generation of subpopulations of procoagulant platelets2014Konferansepaper (Fagfellevurdert)
  • 22.
    Andraos, R.
    et al.
    Linköping University, Linköping, Sweden.
    Södergren, A.L.
    Linköping University, Linköping, Sweden.
    Öllinger, K.
    Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Linköping University, Linköping, Sweden.
    Reactive oxygen species enhance generation of subpopulations of procoagulant platelets2014Konferansepaper (Fagfellevurdert)
  • 23.
    Andrén, O.
    et al.
    Departments of Ecology and Environmental Research, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Barley straw decomposition with varied levels of microbial grazing by Folsomia fimetaria (L.) (Collembola, Isotomidae)1985Inngår i: Oecologia, ISSN 0029-8549, E-ISSN 1432-1939, Vol. 68, nr 1, s. 57-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Folsomia fimetaria (L.) were added (0, 5, 10, 20 animals) to 0.100 g barley straw which had been inoculated 10 days (244 h) earlier with a natural soil microflora. Respiration (CO2 evolution) was monitored continuously. Mass loss, fungal standing crop (total and FDA-active), bacterial and protozoan biomass were estimated 42 days (1,000 h) after microbial inoculation. The degree of surface cover by hyphae was surveyed at regular intervals. No significant differences (P>0.05) were found in respiration, mass loss or microbial biomass, but the density of surface hyphae were reduced by addition of Collembola. Fungal production was low, less than 5% of the estimated microbial production, and could not account for all collembolan growth during incubation. F. fimetaria appeared to consume mainly bacteria and protozoa, and had little impact on carbon mineralization.

  • 24.
    Arinell, Karin
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Sahdo, Berolla
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Evans, Alina L.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Evenstad, Norway; Section of Arctic Veterinary Medicine, Norwegian School of Veterinary Science, Tromsø, Norway.
    Arnemo, Jon M.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Evenstad, Norway; Department of Wildlife Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Baandrup, Ulrik
    Department of Pathology, Vendsyssel Hospital, Hjørring, Denmark; Faculty of Medical Sciences, Aalborg, Denmark.
    Fröbert, Ole
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis Despite Highly Elevated Plasma Lipids during Hibernation and Active State2012Inngår i: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 5, nr 3, s. 269-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free-ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free-ranging brown bears (three females, 23 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.512 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 +/- 1.04 mmol/L vs. 7.89 +/- 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 +/- 0.62 mmol/L vs. 1.44 +/- 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 +/- 0.71 mmol/L vs. 2.02 +/- 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of -atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance.

  • 25.
    Aronson, D.
    et al.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Wojtaszewski, J.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Thorell, A.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Nygren, J.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Zangen, A.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Richter, E. A.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Fielding, R. A.
    Department of Health Sciences, Sargent Coll. All. Hlth. Professions, Boston University, Boston, MA , United States.
    Goodyear, L. J.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Joslin Diabetes Center, One Joslin Place, Boston, MA, United States.
    Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle1998Inngår i: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 275, nr 2, s. C555-C561Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.

  • 26.
    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 activation1994Inngår i: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 14, nr 10, s. 6715-6726Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 27.
    Asghar, Naveed
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gunaltay, Sezin
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Tran, Pham Tue Hung
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    DNA launched suicidal flaviviruses as therapeutic vaccine candidates2018Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. The relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect interventions with high efficiency. We aim to develop therapeutic vaccine candidates against HBV, HCV and HDV using DNA based subgenomic flavivirus replicons as a delivery system. Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), or Kunjinvirus (KUNV) replicon with firefly luciferase geneas a reporter were expressed and characterized in cell culture studies. WNV and KUNV replicons showed significantly higher replication compared to their respective negative controls with unfunctional viral RNA dependent RNA polymerase. KUNV and WNV replicons were chosen for cloning the HCV or HB/DV vaccine candidate gene by replacing luciferasegene. Owing to the self-replicating trait of the flavivirus subgenomic replicons, Western blotting demonstrated that the antigen expression by KUNV and WNV replicons was several folds higher than the positive control. These results suggest that DNA based KUNV and WNV replicons may function as carriers for the hepatitis vaccine candidate genes, and these replicons are currently used for in vivostudies in animal models.

  • 28.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden .
    Lee, Yi-Ping
    Department of Clinical Microbiology, Virology,Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Nilsson, Emma
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Kröger, Andrea
    Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany; Institute for Microbiology, University of Magdeburg, Magdeburg, Germany.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 39265Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Torö-2003 with the wild-type (A)3C(A)6 sequence (Torö-6A) or with a modified (A)3C(A)38 sequence (Torö-38A). Torö-38A replicated poorly compared to Torö-6A in cell culture, but Torö-38A was more virulent than Torö-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

  • 29.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases, Linköping University Hospital, Linköping, Sweden.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Medical Services, Department of Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för läkarutbildning. School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden; RiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, artikkel-id e103264Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 30.
    Asghar, Naveed
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Maravelia, Panagiota
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tran, Pham Tue Hung
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Pasetto, Anna
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlen, Gustaf
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, as cured patients can be re-infected they lack protective immune responses. In addition, the relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We therefore have developed DNA based flavivirus replicons as a potent delivery system that effectively prime HCV-specific T cell responses. We generated suicidal subgenomic DNA replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjinvirus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression by standard DNA plasmid with CMV promoter. The immunogenicity of three suicidal flaviviral DNA replicons expressing HCV NS3/4A was tested in mice and compared to HCV NS3/4A expression by the standard DNA plasmid. The KUNV-HCV replicon was the best replicon-based immunogen with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, dextramer staining, and polyfunctionality. Importantly, a mutant KUNV-HCV immunogen lacking replication failed to induce immune responses. Thus, the newly developed KUNV-based suicidal DNA launched replicon vaccine for HCV is a highly attractive candidate as a prophylactic vaccine against chronic hepatitis C. In addition, we are currently testing the immunogenicity of KUNV-HB/DV replicon in mice.

  • 31.
    Asghar, Naveed
    et al.
    Södertörns Högskola, Huddinge, Sweden.
    Wessam, Melik
    Södertörns Högskola, Huddinge, Sweden.
    Lindblom, Pontus
    Linköpings Universitet, Linköping, Sweden.
    Lindgren, Per-Erik
    Linköpings Universitet, Linköping, Sweden.
    Andreassen, Åshild
    Norska folkhälsoinstitutet, Oslo, Norway.
    Johansson, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro universitet, Institutionen för läkarutbildning.
    Genomic Sequencing of Tick-borne Encephalitis Virus frin Questing and Blood-Feeding Ixodes ricinus2013Konferansepaper (Annet vitenskapelig)
  • 32.
    Asherson, Philip
    et al.
    MRC SGDP Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Family, twin, and adoption studies of childhood onset psychiatric and neurodevelopmental disorders2016Inngår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 171, nr 7, s. 923-924Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Asnake, Solomon
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Interaction of brominated flame retardants with the chicken and zebrafish androgen receptors2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The survival of organisms depends on their ability to use different signaling pathways to adapt to the environment. The endocrine system consists of glands that release hormones to the blood stream. Male reproductive functions are regulated by androgens through interactions with the androgen receptor (AR). AR has been characterized in chicken and zebrafish where they use testosterone and 11-ketotestosterone as their primary androgens, respectively. AR function has been disturbed by different endocrine disrupting compounds (EDCs) present in the environment causing detrimental effects on avian and fish species. Brominated flame retardants (BFRs) are a group of EDCs that are ubiquitous in the environment. Molecular modeling techniques using computer simulations such as docking and molecular dynamics are a useful tool in the identification of EDCs. The capacity to test thousands of compounds at once has helped in the early identification of EDCs that interact with AR. Two groups of BFRs, the 1,2-dibromo-4- cyclohexane diastereomers (TBECH) and the compounds synthesized from 2, 4, 6-tribromophenol, allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6- tribromophenyl ether (BATE) and 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE) interact and alter AR activity in human in vitro studies. As models for avian and fish species, chicken and zebrafish were used to test these BFRs. TBECH diastereomers were able to bind to the AR, estrogen receptors and thyroid receptors in the chicken and to the AR in zebrafish. ATE, BATE and DPTE were also able to interact with the chicken AR and zebrafish AR. Activation studies using cell lines showed that TBECH diastereomers acted as agonists to the cAR and zAR while ATE, BATE and DPTE acted as antagonists. The BFRs also altered multiple signaling pathways such as the apoptotic, antiapoptotic, immune, drug metabolizing and DNA methylation systems and in vivo studies resulted in physiological effects on zebrafish.

    Delarbeid
    1. 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells
    Åpne denne publikasjonen i ny fane eller vindu >>1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells
    Vise andre…
    2014 (engelsk)Inngår i: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 33, nr 4, s. 891-899Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The incorporation of brominated flame retardants into industrial and household appliances has increased their occurrence in the environment, resulting in deleterious effects on wildlife. With the increasing restraints on available compounds, there has been a shift to using brominated flame retardants that has seen the production of alternative brominated flame retardants such as 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH), which has been detected in the environment. In previous in silico and in vitro studies the authors have shown that TBECH can activate both the human androgen receptor (hAR) and the zebrafish AR (zAR) suggesting that it is a potential endocrine disruptor. The present study was aimed at determining the interaction of TBECH with the chicken AR (cAR). In the present study, TBECH bound to cAR, but in vitro activation assay studies using the chicken LMH cell line showed it had a potency of only 15% compared with testosterone. Sequence difference between ARs from different species may contribute to the different responses to TBECH. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that TBECH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that TBECH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. This demonstrates that TBECH, apart from activating cAR, can also influence multiple biological pathways in the chicken.

    sted, utgiver, år, opplag, sider
    Hoboken: Wiley-Blackwell, 2014
    Emneord
    Endocrine disruptor, Diastereomer, Enantiomer, Quantitative polymerase chain reaction (qPCR), Gene regulation
    HSV kategori
    Forskningsprogram
    Miljövetenskap; Biologi
    Identifikatorer
    urn:nbn:se:oru:diva-34941 (URN)10.1002/etc.2509 (DOI)000333538700020 ()2-s2.0-84897431931 (Scopus ID)
    Forskningsfinansiär
    Swedish Research Council
    Merknad

    Funding Agency:

    Örebro University

    Tilgjengelig fra: 2014-05-05 Laget: 2014-05-05 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    Åpne denne publikasjonen i ny fane eller vindu >>The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    2013 (engelsk)Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 142, s. 63-72Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism. In silica modeling demonstrated that TBECH diastereomers bind to the zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH has androgenic properties. Deleterious effects of TBECH were studied on embryonic and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to determine TBECH effects on gene regulation. TBECH was found to delay hatching at 1 mu M and 10 mu M doses while morphological abnormalities and juvenile mortality was observed at 10 mu M. The qRT-PCR analysis showed alterations of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response. Thus, TBECH induces androgenic activity and has negative effects on zebrafish physiology and therefore its impact on the environment should be carefully monitored. (C) 2013 Elsevier B.V. All rights reserved.

    Emneord
    Androgens, Endocrine, Endocrine disruptor, Gene regulation
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-32902 (URN)10.1016/j.aquatox.2013.07.018 (DOI)000328093900007 ()23958786 (PubMedID)
    Forskningsfinansiär
    Knowledge Foundation
    Tilgjengelig fra: 2014-01-02 Laget: 2014-01-02 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3. The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cells
    Åpne denne publikasjonen i ny fane eller vindu >>The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cells
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    EDC, Avian, signaling pathways, ATE, BATE, DPTE, TBECH
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-43909 (URN)
    Tilgjengelig fra: 2015-03-27 Laget: 2015-03-27 Sist oppdatert: 2017-10-17bibliografisk kontrollert
    4. In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish
    Åpne denne publikasjonen i ny fane eller vindu >>In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    Brominated flame retardants, stereoidgenesis, gene regulation, hatch, teratogenesis
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-43911 (URN)
    Tilgjengelig fra: 2015-03-27 Laget: 2015-03-27 Sist oppdatert: 2017-10-17bibliografisk kontrollert
  • 34.
    Asnake, Solomon
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Modig, Carina
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Species differences in ligand interaction and activation of estrogen receptors in fish and human2019Inngår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 195, artikkel-id 105450Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 35.
    Asnake, Solomon
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Pradhan, Ajay
    Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden.
    Kharlyngdoh, Joubert Banjop
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Modig, Carina
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells2015Inngår i: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 29, nr 8, s. 1993-2000Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, ally1-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropy1-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyI-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR. In silico modeling studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the chicken AR ligand-binding pocket. In vitro transfection assays revealed that all three brominated compounds acted as chicken AR antagonists, inhibiting testosterone induced AR activation. In addition, qRT-PCR studies confirmed that they act as AR antagonists and demonstrated that they also alter gene expression patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE, TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken.

  • 36.
    Asnake, Solomon
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Pradhan, Ajay
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Kharlyngdoh, Joubert Banjop
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cellsManuskript (preprint) (Annet vitenskapelig)
  • 37.
    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 universitet, Institutionen för naturvetenskap och teknik. 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 universitet, Institutionen för medicinska vetenskaper. 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 vitro2011Inngår i: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 7, nr 2, s. 437-446Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 38.
    Aydin, Ayhan
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Påverkas smaken på höns av foder, genmaterial och tillagningsmetoder?2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Få produkter i Sverige innehåller idag höns däremot ökar konsumtionen av ägg. Den ojämna balansen mellan ökad äggproduktion och minskad konsumtion av höna tycks vara en uppåtgående trend. Höns som livsmedel har utgått i det ordinarie sortimentet hos de stora livsmedelskedjorna. Livsmedelsproducenter har slutat använda höns på grund av ”kvalitetsbrister” som att de har fått skört skelett. I och med det kan benflisor komma med i köttet. Huvudsakligen är hönsen avlade för att producera mycket ägg - ett om dagen, i stora grupper. Dessa djur är anpassade för storskalig produktion med många djur på en liten yta. Den separering som skett mellan slaktkycklingar och värphöns med början på 1920-talet kan varit en del av förklaringen med minskad hönskötts konsumtion. Hos äldre djur finns det mer bindväv och fettansamling. Den ökade mängden bindväv gör att konsistensen på köttet uppfattas segare men också saftigare, då fett ansamlas där. Substanserna som finns i fettvävnaden, ger upphov till den karaktäristiska smaken och aromen som finns i köttet. Det blir tydligare vid upphettning. När ett djur blir äldre ökar mängden bindväv och dess tvärbindningar, som både stabiliserar men även blir mer värmetåliga. Desto mer ett djuret rör på sig, blir de röda muskelfibrerna aktiva och bildar en grövre struktur. Åldern tillsammans med rörelse kan också skapa ett mer smakrikt kött men även ett segare kött av större fibrer i bindväven som behöver längre tillagningstid.

    I denna studie undersöktes smak samt textur av foder och genmaterial med två olika tillagningsmetoder, kokning samt sous-vide. En panel utvärderade det utifrån 13 variabler. Där det fanns en tydligast signifikans var skillnaden mellan lår och bröst. Att dela upp höns i bröst och lår/vingar gör att förutsättningarna för en mer exakt tillagning ökar. De variabler som hade en signifikans när en PCA-analys gjordes var: textur: saftighet, fethet; smak: härsken; doft: umami, härsket. När t-test utfördes blev det signifikans på saftighet, fethet, smak av härsket och doften av umami. Variablerna som tydligast skilde sig åt mellan bröst och lår var texturerna, saftighet och fethet. Det var ingen signifikant skillnad mellan genotyperna, tillagning eller foder.

  • 39. Bahr, Adam
    et al.
    Ellström, Magnus
    Akselsson, Cecilia
    Ekblad, Alf
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Mikusinska, Anna
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Wallander, Håkan
    Growth of ectomycorrhizal fungal mycelium along a Norway spruce forest nitrogen deposition gradient and its effect on nitrogen leakage2013Inngår i: Soil Biology and Biochemistry, ISSN 0038-0717, E-ISSN 1879-3428, Vol. 59, s. 38-48Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Almost all boreal and temperate forest tree species live in symbiosis with ectomycorrhizal fungi (EMF); the trees transfer carbon (C) to the fungi in exchange for nutrients and water. Several studies have shown that experimental application of inorganic nitrogen (N) represses production of EMF extramatrical mycelia (EMM), but studies along N deposition gradients are underrepresented. Other environmental variables than N may influence EMM production and in this study we included 29 thoroughly monitored Norway spruce stands from a large geographical region in Sweden in order to evaluate the importance of N deposition on EMM growth and N leaching in a broader context. It was concluded that N deposition was the most important factor controlling EMM production and that the amounts typically deposited in boreal and boreo-nemoral regions can be sufficient to reduce EMM growth. Other factors, such as phosphorus status and pH, were also correlated with EMM production and should be considered when predicting EMM growth and N leaching. We also showed that EMM production substantially contributed to the C sequestration (320 kg ha(-1) yr(-1)), suggesting that it should be included in C cycle modelling. Furthermore, EMF are probably important for the N retention capacity since high N leaching coincided with low EMM growth. However, it was not possible to differentiate between the effects of EMF and the direct effect of N deposition on N leaching in the present study.

  • 40.
    Baker, Laura
    et al.
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Tuvblad, Catherine
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Wang, Pan
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Gomez, Karina
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Bezdjian, Serena
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Niv, Sharon
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Raine, Adrian
    Departments of Criminology and Psychiatry, University of Pennsylvania, Philadelphia PA, United States .
    The southern california twin register at the University of Southern California: III2013Inngår i: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 16, nr 1, s. 336-343Artikkel i tidsskrift (Fagfellevurdert)
  • 41.
    Baker, Laura
    et al.
    University of Southern California, Los Angeles, USA.
    Tuvblad, Catherine
    University of Southern California, Los Angeles, USA.
    Wang, Pan
    University of Southern California, Los Angeles, USA.
    Younan, Diana
    University of Southern California, Los Angeles, USA.
    Franklin, Meredith
    University of Southern California, Los Angeles, USA.
    Lurman, Fred
    Sonoma Technology Inc, Petaluma, USA.
    Wu, Jun
    Irvine College of Health Sciences, University of California, Irvine, USA.
    Chen, Jiu-Chiuan
    University of Southern California, Los Angeles, USA.
    The Relationship between IQ and PM2.5: Findings from the University of Southern California Twin Study2016Inngår i: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 46, nr 6, s. 772-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We examined the longitudinal relationship between IQ and fine particulate matter (\2.5lm aerodynamic diameters; PM2.5) exposure in urban-dwelling children, using prospective longitudinal data from the USC Twin Study of Risk Factors for Antisocial Behavior (RFAB; Baker et al. 2013). Residential addresses were collected via selfreports. Verbal and Performance IQ during childhood (age 9–10) and young adulthood (age 19–20) were evaluated by the Wechsler Abbreviated Intelligence Scale (Wechsler, 1999) using four subtests: VIQ=Vocabulary Similarities; PIQ=Block Design Matrices. Based on residential addresses and spatiotemporal generalized additive model of local monitoring data for PM2.5, we estimated 1-year average exposure before each assessment. A three-level mixed effects model regressing IQ scores at each assessment on time-varying air pollution exposures, accounting for both within-family (random intercepts) and within-individual (random slopes) was used. PM2.5 exposure had significant adverse effects on PIQ (95 % CI of b:-7.29 to-1.01, p\.05) but not VIQ (95 % CI of b:-4.50 to-1.96). Adverse effects of PM2.5 exposure remained significant after adjusting for age, family SES, sex, race/ethnicity, parental cognitive abilities, neighborhood SES, neighborhood quality and neighborhood greenness; the association was still significant after further adjusting for traffic distance (300 m), temperature, humidity and annual NOx. PM2.5 exposure confers stronger adverse effects on PIQ in low SES families, males, and during pre-adolescence. Our findings reveal social disparities and sexual dimorphism in the adverse PM2.5 exposure effects on PIQ. Baker, L., Tuvblad, C., Wang, P., Gomez, K., Bezdjian, S., Niv, S., & Raine, A. (2013). The Southern California Twin Register at the University of Southern California: III. Twin Research and Human Genetics, 16(1), 336–343; Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence (WASI). San Antonio, Texas: Harcourt Assessment.

  • 42.
    Balcha, Ermias Sissay
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    C10X Polymorphism in the CARD8 gene is Associated with Bacteremia2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 43.
    Bang, Charlotte Sahlberg
    et al.
    Örebro universitet, Institutionen för hälsovetenskaper.
    Demirel, Isak
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Kruse, Robert
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Persson, Katarina
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 6, artikkel-id e0178541Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim. This study identifies several enriched gene ontologies, modified pathways and single genes that are targeted by CORM-2 in a multidrug-resistant UPEC isolate. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the susceptibility to CORM-2 remained after repeated exposure.

  • 44.
    Bang, Charlotte Sahlberg
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Kinnunen, Annica
    IRiSC, Fac Med & Hlth, Univ Örebro, Örebro, Sweden.
    Karlsson, Marie
    IRiSC, Fac Med & Hlth, Univ Örebro, Örebro, Sweden.
    Önnberg, Anna
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Dept Lab Med, Örebro Univ Hosp, Örebro, Sweden.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Persson, Katarina
    Örebro universitet, Institutionen för läkarutbildning.
    The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide2014Inngår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 14, artikkel-id 65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin.

    Results: Four clinical isolates of multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h.

    Conclusion: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.

  • 45.
    Banjop Kharlyngdoh, Joubert
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Modulation of androgen receptor function by brominated flame retardants2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Delarbeid
    1. Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters
    Åpne denne publikasjonen i ny fane eller vindu >>Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters
    Vise andre…
    2015 (engelsk)Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 74, s. 60-70Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5. α-reductases and β-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5. α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE and DPTE are potent AR antagonists and the alterations in LAT gene transcription suggest that these compounds can affect neuronal functions and should be considered as potential neurotoxic and endocrine disrupting compounds.

    Emneord
    Gene regulation; Human; PSA; LAT
    HSV kategori
    Forskningsprogram
    Biologi
    Identifikatorer
    urn:nbn:se:oru:diva-41508 (URN)10.1016/j.envint.2014.09.002 (DOI)000346681700008 ()25454221 (PubMedID)2-s2.0-84908626070 (Scopus ID)
    Forskningsfinansiär
    Knowledge Foundation, 20110183
    Merknad

    Funding Agency:

    Örebro University J61900

    Tilgjengelig fra: 2015-01-14 Laget: 2015-01-14 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    Åpne denne publikasjonen i ny fane eller vindu >>The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    2013 (engelsk)Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 142, s. 63-72Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism. In silica modeling demonstrated that TBECH diastereomers bind to the zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH has androgenic properties. Deleterious effects of TBECH were studied on embryonic and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to determine TBECH effects on gene regulation. TBECH was found to delay hatching at 1 mu M and 10 mu M doses while morphological abnormalities and juvenile mortality was observed at 10 mu M. The qRT-PCR analysis showed alterations of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response. Thus, TBECH induces androgenic activity and has negative effects on zebrafish physiology and therefore its impact on the environment should be carefully monitored. (C) 2013 Elsevier B.V. All rights reserved.

    Emneord
    Androgens, Endocrine, Endocrine disruptor, Gene regulation
    HSV kategori
    Identifikatorer
    urn:nbn:se:oru:diva-32902 (URN)10.1016/j.aquatox.2013.07.018 (DOI)000328093900007 ()23958786 (PubMedID)
    Forskningsfinansiär
    Knowledge Foundation
    Tilgjengelig fra: 2014-01-02 Laget: 2014-01-02 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3. Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomers
    Åpne denne publikasjonen i ny fane eller vindu >>Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomers
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    steroid hormone receptor, endocrine disruptor, human carcinoma, androgen agonists
    HSV kategori
    Forskningsprogram
    Biologi
    Identifikatorer
    urn:nbn:se:oru:diva-44665 (URN)
    Tilgjengelig fra: 2015-05-20 Laget: 2015-05-20 Sist oppdatert: 2017-10-17bibliografisk kontrollert
    4. Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptor
    Åpne denne publikasjonen i ny fane eller vindu >>Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptor
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Emneord
    DBE-DBCH/TBECH, TBP-AE/ATE, TBP-BAE/BATE, TBP-DBPE/DPTE, endocrine disruptors, PSA, steroidogenesis
    HSV kategori
    Forskningsprogram
    Biologi
    Identifikatorer
    urn:nbn:se:oru:diva-44666 (URN)
    Tilgjengelig fra: 2015-05-20 Laget: 2015-05-20 Sist oppdatert: 2017-10-17bibliografisk kontrollert
  • 46.
    Banjop Kharlyngdoh, Joubert
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptorManuskript (preprint) (Annet vitenskapelig)
  • 47.
    Banjop Kharlyngdoh, Joubert
    et al.
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Pradhan, Ajay
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Asnake, Solomon
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Olsson, Per-Erik
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomersManuskript (preprint) (Annet vitenskapelig)
  • 48.
    Barnes, Paul W.
    et al.
    Loyola University, New Orleans, USA.
    Morales, Luis Orlando
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Robson, T. M.
    University of Helsinki, Helsinki, Finland.
    The importance and direction of current and future plant-UV research2018Inngår i: UV4Plants Bulletin, ISSN 2343-323X, Vol. 2, s. 19-32Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 49.
    Basabe-Desmonts, L.
    et al.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland; Biomedical Diagnostics Institute Programme, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Ramström, Sofia
    Biomedical Diagnostics Institute Programme, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Lopez-Alonso, A.
    Biomedical Diagnostics Institute Programme, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Somers, M.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland.
    Ricco, A. J.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland.
    Kenny, D.
    Biomedical Diagnostics Institute Programme, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Disposable bioanalytical microdevice for monitoring the effect of anti-platelet drugs2010Inngår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010, 2010, s. 1388-1390Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We report a disposable self-powered integrated microfluidic chip that enables a rapid and simple platelet-function assay from small samples of whole blood. The chip integrates a single-cell adhesion assay with a microfluidic platform; it enables accurate quantification of platelet adhesion, and it controls whole blood flow rate, shear stress, volume of sample, and assay time.

  • 50.
    Basabe-Desmonts, L.
    et al.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland.
    Ramström, Sofia
    BDI Programme, Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Meade, G.
    BDI Programme, Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    O'Neill, S.
    BDI Programme, Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Riaz, A.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland.
    Lee, L. P.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland; Biomolecular Nanotechnology Center, Berkeley Sensor & Actuator Center, Department of Bioengineering, University of California, Berkeley CA, USA.
    Ricco, A. J.
    Biomedical Diagnostics Institute (BDI), Dublin City University, Dublin, Ireland.
    Kenny, D.
    BDI Programme, Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
    Single-Step Separation of Platelets from Whole Blood Coupled with Digital Quantification by Interfacial Platelet Cytometry (iPC)2010Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 26, nr 18, s. 14700-14706Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates By separating platelets From whole blood using specific binding to protein spots of a defined size. iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (I) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopuladons from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated To date, we have demonstrated 1-4 of the above list Platelets were separated from whole blood using tPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 full) The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (aIlb beta 3) and, relevant to diagnostic applications, platelet adhesion correlates strongly with normal versus abnormal platelet function A critical function of platelets is to adhere to regions of damage on blood vessel walls, in contrast to conventional flow cytometry, where platelets are suspended in solution, iPC enables physiologically relevant platelet bioassays based on platelet/protein-matrix inter actions on surfaces. This technology should be inexpensive to implement in clinical assay format, is readily integrable into fluidic microdevices, and paves the way for high-throughput platelet assays from microliter volumes of whole blood.

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