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  • 51.
    Delsing, Louise
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Hicks, Ryan
    IMED Discovery Sciences, AstraZeneca, Mölndal, Sweden.
    Zetterberg, Henrik
    University of Gothenburg, Gothenburg, Sweden.
    Human iPSC-derived endothelial cells can develop in to brain-like endothelial cells after coculture with primary human brain cells2017Conference paper (Refereed)
  • 52.
    Deo, Ameya
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Carlsson, Jessica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lindlof, Angelica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    HOW TO CHOOSE A NORMALIZATION STRATEGY FOR MIRNA QUANTITATIVE REAL-TIME (QPCR) ARRAYS2011In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 9, no 6, p. 795-812Article in journal (Refereed)
    Abstract [en]

    Low-density arrays for quantitative real-time PCR (qPCR) are increasingly being used as an experimental technique for miRNA expression profiling. As with gene expression profiling using microarrays, data from such experiments needs effective analysis methods to produce reliable and high-quality results. In the pre-processing of the data, one crucial analysis step is normalization, which aims to reduce measurement errors and technical variability among arrays that might have arisen during the execution of the experiments. However, there are currently a number of different approaches to choose among and an unsuitable applied method may induce misleading effects, which could affect the subsequent analysis steps and thereby any conclusions drawn from the results. The choice of normalization method is hence an important issue to consider. In this study we present the comparison of a number of data-driven normalization methods for TaqMan low-density arrays for qPCR and different descriptive statistical techniques that can facilitate the choice of normalization method. The performance of the normalization methods was assessed and compared against each other as well as against standard normalization using endogenous controls. The results clearly show that the data-driven methods reduce variation and represent robust alternatives to using endogenous controls.

  • 53.
    Desale, Prithviraj
    et al.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, India.
    Kashyap, Deboleena
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, India.
    Nawani, Neelu
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, India.
    Nahar, Noor
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kapadnis, Balasaheb
    University of Pune, India.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Biosorption of nickel by Lysinibacillus sp. BA2 native to bauxite mine2014In: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 107, p. 260-268Article in journal (Refereed)
    Abstract [en]

    The current scenario of environmental pollution urges the need for an effective solution for toxic heavy metal removal from industrial wastewater. Bioremediation is the most cost effective process employed by the use of microbes especially bacteria resistant to toxic metals. In this study, Lysinibacillus sp. BA2, a nickel tolerant strain isolated from bauxite mine was used for the biosorption of Ni(II). Lysinibacillus sp. BA2 biomass had isoelectric point (pI) of 3.3. The maximum negative zeta potential value (−39.45) was obtained at pH 6.0 which was highly favourable for Ni(II) biosorption. 238.04 mg of Ni(II) adsorbed on one gram of dead biomass and 196.32 mg adsorbed on one gram of live biomass. The adsorption of Ni(II) on biomass increased with time and attained saturation after 180 min with rapid biosorption in initial 30 min. The Langmuir and Freundlich isotherms could fit well for biosorption of Ni(II) by dead biomass while Langmuir isotherm provided a better fit for live biomass based on correlation coefficient values. The kinetic studies of Ni(II) removal, using dead and live biomass was well explained by second-order kinetic model. Ni(II) adsorption on live biomass was confirmed by SEM-EDX where cell aggregation and increasing irregularity of cell morphology was observed even though cells were in non-growing state. The FTIR analysis of biomass revealed the presence of carboxyl, hydroxyl and amino groups, which seem responsible for biosorption of Ni(II). The beads made using dead biomass of Lysinibacillus sp. BA2 could efficiently remove Ni(II) from effluent solutions. These microbial cells can substitute expensive methods for treating nickel contaminated industrial wastewaters.

  • 54.
    Desale, Prithviraj
    et al.
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Mumbai-Pune Expressway, Survey No. 87/88, Tathawade, Pune 411033, India.
    Prakash, Divya
    Department of Microbiology, University of Pune, Pune 41107. India.
    Keyur, Patel
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Mumbai-Pune Expressway, Survey No. 87/88, Tathawade, Pune 411033, India.
    Rupali, Aursang
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Mumbai-Pune Expressway, Survey No. 87/88, Tathawade, Pune 411033, India.
    Nawani, Neelu
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Mumbai-Pune Expressway, Survey No. 87/88, Tathawade, Pune 411033, India.
    Kapadnis, Balasaheb
    Department of Microbiology, University of Pune, Pune 41107. India.
    Khetmalas, Madhukar
    Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Mumbai-Pune Expressway, Survey No. 87/88, Tathawade, Pune 411033, India.
    Mandal, Abul
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Biosorption of Heavy Metals by Actinomycetes for Treatment of Industrial Effluents2012In: / [ed] Buhri Arifin, Siti Nur`Afifah Jaafar, Sayed Mohamed Zain S. Hasan, Anuar Hassan, H. M. Edi Armanto, Chuah Tse Seng, Wan Zaliha Wan Sembok, Shahreza Md Sheriff, Suparjo Noordin Mokhtar, Fazlil Ilahi Abdul Wahab, Hayati Mohd Yusof, Adzemi Mat. Arshad, Universiti Malaysia Terengganu , 2012, p. 389-393Conference paper (Refereed)
    Abstract [en]

    Rapid industrialization usually is the cause of increase in pollutants in the natural river bodies. This pollution is attributed to lack of improper treatment and inadequate disposal mechanisms of the waste generated thereof. The aim of present investigation was to screen actinomycetes for their ability to adsorb heavy metals. Actinomycetes belong to most diverse group of filamentous prokaryotes with ubiquitous presence in different ecological niches. This ubiquity is due to their ability to degrade almost any type of polymer and to use several compounds as carbon sources. Nearly 200 actinomycetes from different niches like fresh water, soda lake, geothermal springs, acid soils, etc from different locations in India were screened for ability to grow in presence of 1 to 5 mM of heavy metals like Cd, Hg, Pb, Ni, Sr, Fe, Mo, Zn and Mn. Most of the strains tolerant to heavy metals belonged to the genus Streptomyces spp. Five strains could grow in presence of 5 mM Cd2+, 4 strains in presence of 0.1 mM Hg2+, 18 strains in presence of 5 mM Pb2+, 21 strains in presence of 5 mM Ni2+, whereas 34 strains grew in presence of 5 mM Fe2+. One of the most promising strain was studied for its ability to absorb cadmium where 2x1011 cells or spores could adsorb 0.32 mM to 0.33 mM of cadmium. Spores and vegetative cells showed nearly similar level of adsorbtion ability. This strain can be very useful in developing a bioreactor for the adsorption of heavy metals from industrial effluents containing cadmium.

  • 55.
    Dewdney, Chris
    et al.
    University of Portsmouth, Portsmouth, UK.
    Pylkkänen, Paavo
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Basil Hiley Festschrift Introduction2013In: Foundations of physics, ISSN 0015-9018, E-ISSN 1572-9516, Vol. 43, no 4, p. 409-411Article in journal (Other academic)
  • 56.
    Dewdney, Chris
    et al.
    University of Portsmouth, Portsmouth, UK.
    Pylkkänen, PaavoUniversity of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.Atmanspacher, Harald
    Basil Hiley Festschrift2013Collection (editor) (Other academic)
  • 57.
    Doktorova, Tatyana Y.
    et al.
    Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium.
    Yildirimman, Reha
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
    Vinken, Mathieu
    Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium.
    Vilardell, Mireia
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
    Vanhaecke, Tamara
    Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium.
    Gmuender, Hans
    Genedata AG, Basel, Switzerland.
    Bort, Roque
    Unit of Experimental Hepathology, University Hospital La Fe Valencia, Spain / Faculty of Medicine, Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain.
    Brolen, Gabriella
    Cellectis, Göteborg, Sweden.
    Holmgren, Gustav
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Cellectis, Göteborg, Sweden.
    Li, Ruoya
    Biopredic International, Rennes, France.
    Chesne, Christophe
    Biopredic International, Rennes, France.
    van Delft, Joost
    Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
    Kleinjans, Jos
    Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
    Castell, Jose
    Unit of Experimental Hepathology, University Hospital La Fe Valencia, Spain / Faculty of Medicine, Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain.
    Björquist, Petter
    Cellectis, Göteborg, Sweden.
    Herwig, Ralf
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
    Rogiers, Vera
    Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Brussels, Belgium.
    Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models2013In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, no 6, p. 1393-1402Article in journal (Refereed)
    Abstract [en]

    As the conventional approach to assess the potential of a chemical to cause cancer in humans still includes the 2-year rodent carcinogenicity bioassay, development of alternative methodologies is needed. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically stabilized cultures of primary rat hepatocytes, the human hepatoma-derived cell lines HepaRG and HepG2 and human embryonic stem cell-derived hepatocyte-like cells, are examined. For full characterization of the systems, several bioinformatics approaches are employed including gene-based, ConsensusPathDB-based and classification analysis. They provide convincingly similar outcomes, namely that upon exposure to carcinogens, the HepaRG generates a gene classifier (a gene classifier is defined as a selected set of characteristic gene signatures capable of distinguishing GTX, NGTX carcinogens and NC) able to discriminate the GTX carcinogens from the NGTX carcinogens and NC. The other in vitro models also yield cancer-relevant characteristic gene groups for the GTX exposure, but some genes are also deregulated by the NGTX carcinogens and NC. Irrespective of the tested in vitro model, the most uniformly expressed pathways following GTX exposure are the p53 and those that are subsequently induced. The NGTX carcinogens triggered no characteristic cancer-relevant gene profiles in all liver-based in vitro systems. In conclusion, liver-based in vitro models coupled with transcriptomics techniques, especially in the case when the HepaRG cell line is used, represent valuable tools for obtaining insight into the mechanism of action and identification of GTX carcinogens.

  • 58.
    Eero, Margit
    et al.
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Hjelm, Joakim
    Department of Aquatic Resources, Institute of Marine Research, Swedish University of Agricultural Sciences, Lysekil, Sweden.
    Behrens, Jane
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Buchmann, Kurt
    Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark.
    Cardinale, Massimiliano
    Department of Aquatic Resources, Institute of Marine Research, Swedish University of Agricultural Sciences, Lysekil, Sweden.
    Casini, Michele
    Department of Aquatic Resources, Institute of Marine Research, Swedish University of Agricultural Sciences, Lysekil, Sweden.
    Gasyukov, Pavel
    AtlantNIRO, Kaliningrad, Russian Federation.
    Holmgren, Noél
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Horbowy, Jan
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Hüssy, Karin
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Kirkegaard, Eskil
    International Council for the Exploration of the Sea (ICES), Copenhagen, Denmark.
    Kornilovs, Georgs
    Institute of Food Safety, Animal Health and Environment “BIOR”, Riga, Latvia.
    Krumme, Uwe
    Thünen Institute of Baltic Sea Fisheries, Rostock, Germany.
    Köster, Friedrich W.
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Oeberst, Rainer
    Thünen Institute of Baltic Sea Fisheries, Rostock, Germany.
    Plikshs, Maris
    Institute of Food Safety, Animal Health and Environment “BIOR”, Riga, Latvia.
    Radtke, Krzysztof
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Raid, Tiit
    Estonian Marine Institute, University of Tartu, Tallinn, Estonia.
    Schmidt, Jörn
    Department of Economics, Christian-Albrechts University of Kiel, Kiel, Germany.
    Tomczak, Maciej T.
    Stockholm University, Baltic Sea Centre, Stockholm, Sweden.
    Vinther, Morten
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Zimmermann, Christopher
    Thünen Institute of Baltic Sea Fisheries, Rostock, Germany.
    Storr-Paulsen, Marie
    National Institute of Aquatic Resources, Technical University of Denmark, Charlottenlund, Denmark.
    Eastern Baltic cod in distress: biological changes and challenges for stock assessment2015In: ICES Journal of Marine Science, ISSN 1054-3139, E-ISSN 1095-9289, Vol. 72, no 8, p. 2180-2186Article in journal (Refereed)
    Abstract [en]

    The eastern Baltic (EB) cod (Gadus morhua) stock was depleted and overexploited for decades until the mid-2000s, when fishing mortality rapidlydeclined and biomass started to increase, as shown by stock assessments. These positive developments were partly assigned to effective managementmeasures, and the EB cod was considered one of the most successful stock recoveries in recent times. In contrast to this optimistic view, theanalytical stock assessment failed in 2014, leaving the present stock status unclear. Deteriorated quality of some basic input data for stock assessmentin combination with changes in environmental and ecological conditions has led to an unusual situation for cod in the Baltic Sea, which posesnew challenges for stock assessment and management advice.Anumber of adverse developments such as low nutritional condition and disappearanceof larger individuals indicate that the stock is in distress. In this study, we (i) summarize the knowledge of recent changes in cod biology andecosystem conditions, (ii) describe the subsequent challenges for stock assessment, and (iii) highlight the key questions where answers are urgentlyneeded to understand the present stock status and provide scientifically solid support for cod management in the Baltic Sea.

  • 59.
    Ejeskär, Katarina
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Medical and Clinical Genetics, Gothenburg University, Gothenburg, Sweden.
    Vickes, Oscar
    University of Skövde, The Systems Biology Research Centre.
    Kuchipudi, Arunakar
    University of Skövde, The Systems Biology Research Centre.
    Wettergren, Yvonne
    Department of General Surgery, Gothenburg University, Gothenburg, Sweden.
    Uv, Anne
    Department of Medical and Clinical Genetics, Gothenburg University, Gothenburg, Sweden.
    Rotter Sopasakis, Victoria
    Department of Molecular and Clinical Medicine, Institute of Medicine, Wallenberg Laboratory, Gothenburg University, Gothenburg, Sweden.
    The unique non-catalytic C-terminus of p37delta-PI3K adds proliferative properties in vitro and in vivo2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0127497Article in journal (Refereed)
    Abstract [en]

    The PI3K/Akt pathway is central for numerous cellular functions and is frequently deregulated in human cancers. The catalytic subunits of PI3K, p110, are thought to have a potential oncogenic function, and the regulatory subunit p85 exerts tumor suppressor properties. The fruit fly, Drosophila melanogaster, is a highly suitable system to investigate PI3K signaling, expressing one catalytic, Dp110, and one regulatory subunit, Dp60, and both show strong homology with the human PI3K proteins p110 and p85. We recently showed that p37δ, an alternatively spliced product of human PI3K p110δ, displayed strong proliferation-promoting properties despite lacking the catalytic domain completely. Here we functionally evaluate the different domains of human p37δ in Drosophila. The N-terminal region of Dp110 alone promotes cell proliferation, and we show that the unique C-terminal region of human p37δ further enhances these proliferative properties, both when expressed in Drosophila, and in human HEK-293 cells. Surprisingly, although the N-terminal region of Dp110 and the C-terminal region of p37δ both display proliferative effects, over-expression of full length Dp110 or the N-terminal part of Dp110 decreases survival in Drosophila, whereas the unique C-terminal region of p37δ prevents this effect. Furthermore, we found that the N-terminal region of the catalytic subunit of PI3K p110, including only the Dp60 (p85)-binding domain and a minor part of the Ras binding domain, rescues phenotypes with severely impaired development caused by Dp60 over-expression in Drosophila, possibly by regulating the levels of Dp60, and also by increasing the levels of phosphorylated Akt. Our results indicate a novel kinase-independent function of the PI3K catalytic subunit.

  • 60.
    Eklund, Malin B.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Johansson, Linda
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Uvnäs-Moberg, Kerstin
    Department of Animal Environment and Health, Swedish University of Agriculture, P.O. Box 234, SE-532 23 Skara, Sweden.
    Arborelius, Lotta
    Department of Clinical Neuroscience, Division of Psychology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
    Differential effects of repeated long and brief maternal separation on behaviour and neuroendocrine parameters in Wistar dams2009In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 203, no 1, p. 69-75Article in journal (Refereed)
    Abstract [en]

    Repeated, prolonged maternal separation has been suggested to model the development of a depression-like syndrome in rats. The long separations from the pups have been proposed to be stressful for the dams, which in turn could mediate the changes seen in adult offspring. In the present study we investigated whether prolonged maternal separation really is stressful for rat dams by studying parameters known to be affected by long-term stress such as spontaneous motor activity, anxiety-like behaviour, adrenal gland weight and plasma corticosterone levels. Dams were separated from their litter for either 4 h (MS240) or 15 min (MS15) on eight random days during postnatal day 1–14, or left undisturbed (animal facility reared, AFR). After weaning MS240 dams showed decreased peripheral activity and habituated slower in horizontal activity. On the contrary, MS15 dams showed more peripheral activity and less rearing activity compared to both AFR and MS240 dams when habituated to the testing apparatus, suggesting that MS15 dams are more anxious. The adrenal glands from MS15 dams weighed significantly less and plasma corticosterone levels were significantly higher compared to AFR and MS240 dams. These results suggest that repeated brief maternal separations from pups could be stressful for rat mothers, whereas prolonged separations are not. Since these results are in contrast to the current notion that the short separation procedure may be considered as a safe milieu, whereas the prolonged separations have been suggested to be stressful for both dams and pups, further studies in this field are warranted.

  • 61.
    Ekström, Linnéa
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Adolfsson, Annsofie
    Department of Obstetrics and Gynaecology, Skaraborg Hospital, Skövde, Sweden / School of Health and Medical Sciences, University of Örebro, Örebro, Sweden.
    Ericson, Henrik
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Poutakidis, Georgios
    Department of Obstetrics and Gynaecology, Skaraborg Hospital, Skövde, Sweden.
    Charonis, Georgios
    Department of Obstetrics and Gynaecology, University of Linköping, Linköping, Sweden / Mitera General and Maternity Hospital, Athens, Greece.
    Larsson, Per-Göran
    Department of Obstetrics and Gynaecology, Skaraborg Hospital, Skövde, Sweden.
    Vaginal flora and urinary and vaginal group B streptococci in early pregnancy2013In: Gynecology, ISSN 2052-6210, Vol. 1, article id 6Article in journal (Refereed)
    Abstract [en]

    Background: Bacterial vaginosis (BV) is a risk factor for premature birth and group B streptococci (GBS) colonizing the vagina are etiological agents of neonatal infections. Significant growth of GBS in the vagina has been assumed to be detectable through urinary culture. The aim was to investigate the correlation between BV and the presence of GBS in qualitative vaginal or quantitative urinary culture, since this could predict a higher risk for perinatal morbidity. Design and setting: A consecutive prospective study of women in early pregnancy included 3101 women between 2007 and 2010, in a region of south-western Sweden. Methods: Vaginal and urine samples were obtained from women in early pregnancy at maternity health care clinics. BV was diagnosed according to the Ison/Hay classification. GBS in urine were detected in amounts as low as 100 CFU/ml. Vaginal culturing for GBS was obtained from a selected group of 481 women. Results: There was no difference in the prevalence of GBS in the urine among women with BV compared with women with lactobacilli flora (OR 0.7; 95% CI 0.4-1.1). Vaginal presence of GBS was found among 17.3% of women with BV and among 23.5% of women with lactobacilli flora (OR 0.7; 95% CI 0.3-1.4). Among the 105 women who had vaginal GBS, the urine culture of GBS was positive in only 21.9% of cases. Conclusions: Even though women with BV. have much higher concentration of bacteria in the vagina, they do not necessarily have more GBS in the vagina or urine. The modest correlation between positive vaginal culture and positive urine culture of GBS question the value of urinary culture for detection of vaginal GBS.

  • 62.
    Elfstrand Corlin, Tinna
    et al.
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Kajonius, Petri J.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kazemi, Ali
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    The impact of personality on person-centred care: a study of care staff in Swedish nursing homes2017In: International Journal of Older People Nursing, ISSN 1748-3735, E-ISSN 1748-3743, Vol. 12, no 2, article id e12132Article in journal (Refereed)
    Abstract [en]

    Aim and objective: In this study, we explore how personal and situational factors relate to the provision of person-centred care (PCC) in nursing homes. Specifically, we focus on the relationship between the care staff's personality traits and provision of PCC and to what extent perceptions of the working environment influences this relationship.

    Background: The ultimate goal of elderly care is to meet the older person's needs and individual preferences (PCC). Interpersonal aspects of care and the quality of relationship between the care staff and the older person are therefore central in PCC.

    Design and methods: A cross-sectional Swedish sample of elderly care staff (= 322) completed an electronic survey including measures of personality (Mini-IPIP) and person-centred care (Individualized Care Inventory, ICI). A principal component analysis was conducted on the ICI-data to separate the user orientation (process quality) of PCC from the preconditions (structure quality) of PCC.

    Results: Among the five factors of personality, neuroticism was the strongest predictor of ICI user orientation. ICI preconditions significantly mediated this relationship, indicating the importance of a supportive working environment. In addition, stress was introduced as a potential explanation and was shown to mediate the impact of neuroticism on ICI preconditions.

    Conclusions: Personality traits have a significant impact on user orientation, and the perception of a supportive and stress free working environment is an important prerequisite for achieving high-quality person-centred elderly care.

    Implications for practice: Understanding how personality is linked to the way care staff interacts with the older person adds a new perspective on provision of person-centred elderly care.

  • 63.
    Elgbratt, Kristina
    et al.
    Univ Örebro, Sch Hlth & Med Sci, Orebro, Sweden.
    Jansson, Andreas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Hultgren-Hornquist, Elisabeth
    Univ Örebro, Sch Hlth & Med Sci, Orebro, Sweden.
    A Quantitative Study of the Mechanisms behind Thymic Atrophy in G alpha i2-Deficient Mice during Colitis Development2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, p. e36726-Article in journal (Refereed)
    Abstract [en]

    Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.

  • 64.
    Enroth, Helena
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Unilabs AB.
    Engstrand, L.
    Karolinska Institute and Science for Life Laboratory.
    Infectious Diseases: Helicobacter pylori2015In: Reference Module in Biomedical Sciences, Elsevier, 2015Chapter in book (Other academic)
    Abstract [en]

    Abstract Helicobacter pylori infection is one of the most common human infections in the world. The bacteria cause peptic ulcer disease and their infection is an important factor for gastric cancer development. The bacteria are transmitted from person to person within families, with young children most often infected. The bacteria reside in the stomach for a lifetime if untreated by antimicrobial agents. Many virulence factors are known that contribute to the persistence of the bacteria in the stomach, and the bacteria harbors a pathogenicity island in its genome. The discovery of H. pylori as a cause of gastritis in the stomach led to the Nobel Prize in Physiology or Medicine 2005.

  • 65.
    Enroth, Helena
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Retz, Karolina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Carl
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection2019In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 4, p. 249-258Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.

    Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.

    Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.

    Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

  • 66.
    Enroth, Helena
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Unilabs AB.
    Wefer, Hugo
    Clinical genomics, Science for Life Laboratories.
    Ljungström, Lars
    Dept. of Infectious Diseases, Skaraborg Hospital Skövde.
    Tilevik, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    NGS pilot study of E. coli ESBL from patients with suspected sepsis2015Conference paper (Refereed)
  • 67.
    Ericson, Henrik
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Fagerlind, Magnus
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Incorporating Sunflower for Science in teacher education to increase the pedagogical information technology competence of teachers and teacher students in natural science2010In: Society for Information Technology & Teacher Education, 21st International Conference, March 29 - April 2, 2010, Sand Diego, California, USA / [ed] Gibson, D. & Dodge, B., Association for the Advancement of Computing in Education, 2010, p. 463-468Conference paper (Refereed)
    Abstract [en]

    The use of information and communication technology in teaching is an excellent way to visualize processes as well as promote active learning in natural science, hence providing an additional dimension in teaching. KompLIT (Competence Enhancement of Teacher Education Information Technology) is a Swedish project that aims to increase the competence in pedagogical information technology for both teachers and teacher students. As part of this project the software Sunflower for Science has been tested and evaluated by both teachers and teacher students. Sunflower for Science consists of 26 programs in physics, chemistry and biology and uses an interactive approach that engages students with an activity-based learning. The outcome from the evaluation is that Sunflower for Science is very user-friendly, it promotes deeper learning as well as increases the students’ attitude towards chemistry.

  • 68.
    Eriksson, Mats O. G.
    et al.
    MK Natur- och miljökonsult, Lindome, Sweden.
    Paltto, Heidi
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Department of Ecology, Swedish Agricultural University, Uppsala, Sweden.
    Vattenkemi och fiskbeståndens sammansättning i storlommens Gavia arctica häckningssjöar, samt en jämförelse med smålommens Gavia stellata fiskesjöar2010In: Ornis Svecica, ISSN 1102-6812, Vol. 20, no 1, p. 3-30Article in journal (Refereed)
    Abstract [en]

    Breeding  performance  of  Black-throated  Diver  Gavia arctica was compared to water chemistry, light penetration and density of fish in 122 breeding lakes in Sweden with a total of 184 pairs (1.5 pairs per lake, about 3% of the national population). The breeding lakes were on average nutrient-poor, and 12% of them had a low buffering capacity (alkalinity <0.10 meq/l). Perch Perca fluviatilis, roach Rutilus rutilus and pike Esox lucius, three species characteristic for nutrient-poor lakes, were found in more than 90% of the lakes. Salmonid fish occurred in half of the  lakes,  compared  to  >90%  of  the  fishing lakes  used by Red-throated Diver. Reproduction was related to high abundance of Perch, and the survival of chicks to light penetration. Poor nutrient status in combination with low pH or alkalinity in approximatively 10% of the breeding lakes  of  Black-throated  Diver  and  probably  more  than 30% of the fishing lakes of Red-throated Diver, indicate susceptibility  of  exposure  to  methylmercury. This  finding should be considered in relation to recent reports of increased contents of mercury in freshwater fish.

  • 69.
    Fabre, Kristin M.
    et al.
    Microphysiological Systems Center of Excellence, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Waltham, MA, United States.
    Delsing, Louise
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden / Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
    Colclough, Nicola
    Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Crowther, Damian C.
    Neuroscience, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Ewart, Lorna
    Microphysiological Systems Center of Excellence, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Utilizing microphysiological systems and induced pluripotent stem cells for disease modeling: a case study for blood brain barrier research in a pharmaceutical setting2019In: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 140, p. 129-135Article in journal (Refereed)
    Abstract [en]

    Microphysiological systems (MPS) may be able to provide the pharmaceutical industry models that can reflect human physiological responses to improve drug discovery and translational outcomes. With lack of efficacy being the primary cause for drug attrition, developing MPS disease models would help researchers identify novel targets, study mechanisms in more physiologically-relevant depth, screen for novel biomarkers and test/optimize various therapeutics (small molecules, nanoparticles and biologics). Furthermore, with advances in inducible pluripotent stem cell technology (iPSC), pharmaceutical companies can access cells from patients to help recreate specific disease phenotypes in MPS platforms. Combining iPSC and MPS technologies will contribute to our understanding of the complexities of neurodegenerative diseases and of the blood brain barrier (BBB) leading to development of enhanced therapeutics. © 2018

  • 70.
    Fagerlind, Magnus G.
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Webb, Jeremy S.
    Univ Southampton, Sch Biol Sci, Southampton SO16 7PX, Hants, England .
    Barraud, Nicolas
    Univ New S Wales, Ctr Marine Bioinnovat, Sydney, NSW 2052, Australia / Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia .
    McDougald, Diane
    Univ New S Wales, Ctr Marine Bioinnovat, Sydney, NSW 2052, Australia / Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia / Nanyang Technol Univ, Adv Environm Biotechnol Ctr, Singapore 639798, Singapore .
    Jansson, Andreas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nilsson, Patric
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Harlen, Mikael
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Kjelleberg, Staffan
    Univ New S Wales, Ctr Marine Bioinnovat, Sydney, NSW 2052, Australia / Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia / Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore 639798, Singapore .
    Rice, Scott A.
    Univ New S Wales, Ctr Marine Bioinnovat, Sydney, NSW 2052, Australia / Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia / Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore 639798, Singapore .
    Dynamic modelling of cell death during biofilm development2012In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 295, p. 23-36Article in journal (Refereed)
    Abstract [en]

    Biofilms are currently recognised as the predominant bacterial life-style and it has been suggested that biofilm development is influenced by a number of different processes such as adhesion, detachment, mass transport, quorum sensing, cell death and active dispersal. One of the least understood processes and its effects on biofilm development is cell death. However, experimental studies suggest that bacterial death is an important process during biofilm development and many studies show a relationship between cell death and dispersal in microbial biofilms. We present a model of the process of cell death during biofilm development, with a particular focus on the spatial localisation of cell death or cell damage. Three rules governing cell death or cell damage were evaluated which compared the effects of starvation, damage accumulation, and viability during biofilm development and were also used to design laboratory based experiments to test the model. Results from model simulations show that actively growing biofilms develop steep nutrient gradients within the interior of the biofilm that affect neighbouring microcolonies resulting in cell death and detachment. Two of the rules indicated that high substrate concentrations lead to accelerated cell death, in contrast to the third rule, based on the accumulation of damage, which predicted earlier cell death for biofilms grown with low substrate concentrations. Comparison of the modelling results with experimental results suggests that cell death is favoured under low nutrient conditions and that the accumulation of damage may be the main cause of cell death during biofilm development. (C) 2011 Elsevier Ltd. All rights reserved.

  • 71.
    Fagerlind, Magnus
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Stålhammar, Hans
    VikingGenetics, Skara.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Expression of miRNAs in Bull Spermatozoa Correlates with Fertility Rates2015In: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 50, no 4, p. 587-594Article in journal (Refereed)
  • 72.
    Falck, Eva
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Genomic Alterations in Experimental Endometrial Adenocarcinoma2012Licentiate thesis, comprehensive summary (Other academic)
  • 73.
    Falck, Eva
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Genomic and genetic alterations in endometrial adenocarcinoma2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The most frequently diagnosed cancer of the female genital tract is cancer of the endometrium (endometrial cancer), ranking fourth among the invasive tumors that affect women in Europe and North America. As most other cancer types, endometrial cancer is a complex genetic disease influenced by both genetic and environmental factors.

    The human population is genetically heterogeneous and studies of complex diseases in human are proven to be difficult. By using a model system such as the BDII rat, some of the obstacles related to the study of complex diseases can be avoided. The BDII rat strain is prone to spontaneously develop endometrial adenocarcinoma (EAC) and more than 90% of the virgin females develop EAC during their lifetime. Development of EAC tumors in BDII rats is comparable in pathogenesis and histopathological properties to that of human.

    The aims of this thesis were i/ to characterize EAC in the BDII rat experimental model system by analyzing structural and numerical chromosome aberrations, ii/ to evaluate the importance of the genetic set-up in EAC development, and iii/ to determine the impact of genomic and genetic alterations on the functionality of candidate genes in rat EAC and in human endometrial tumors of different FIGO grades.

    Non-random numerical and structural aberrations that could contribute to tumor formation were identified, and evidence that the genetic background had a significant influence on the genome make-up of tumor cells was provided. Certain genes (Gpx3/GPX3, Met/MET, Phf5a/PHF5A, and Gja1/GJA1) were selected for further analysis and aberrant expression of some of them were found in both rat and human EACs. By separating EAC cell lines according to the genetic cross background, for two of the genes (Phf5 and Met), we showed that the expression pattern differed significantly between different cross backgrounds, which clearly pinpoint the importance of using animal models as a complement to clinical studies in identification of cancer-related genes.

  • 74.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    The impact of the genetic background on the genome make-up of tumor cells2012In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 51, no 5, p. 438-446Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most common form of malignancy in the female genital tract, ranking as the fourth leading form of invasive tumors that affect women. The BDII inbred rat strain has been used as a powerful tumor model in studies of the genetic background of EAC. Females from the BDII strain are prone to develop tumors with an incidence of more than 90%. Development of EAC in BDII female rats has similarities in pathogenesis, histopathological, and molecular properties to that of human, and thus represents a unique model for analysis of EAC tumorigenesis and for comparative studies in human EACs. In a previous study, a set of rat EAC cell lines derived from tumors developed in female crossprogenies between BDII and nonsusceptible rat strains were analyzed by spectral karyotyping (SKY). Here we present an analysis with specific focus on the impact of different genetic backgrounds on the rate and occurrence of genetic aberrations in experimental tumors using data presented in the previous report. We could reveal that the ploidy state, and the abundance and type of structural as well as numerical change differed between the two genetic setups. We have also identified chromosomes harboring aberrations independent of genetic input from the nonsusceptible strains, which provide valuable information for the identification of the genes involved in the development of EAC in the BDII model as well as in human endometrial tumors. (C) 2012 Wiley Periodicals, Inc.

  • 75.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Hedberg, Carola
    Univ Gothenburg, Inst Biomed, Dept Med & Clin Genet, SE-40530 Gothenburg, Sweden.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    SKY analysis revealed recurrent numerical and structural chromosome changes in BDII rat endometrial carcinomas2011In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 11, p. 20-Article in journal (Refereed)
    Abstract [en]

    Background: Genomic alterations are common features of cancer cells, and some of these changes are proven to be neoplastic-specific. Such alterations may serve as valuable tools for diagnosis and classification of tumors, prediction of clinical outcome, disease monitoring, and choice of therapy as well as for providing clues to the location of crucial cancer-related genes. Endometrial carcinoma (EC) is the most frequently diagnosed malignancy of the female genital tract, ranking fourth among all invasive tumors affecting women. Cytogenetic studies of human ECs have not produced very conclusive data, since many of these studies are based on karyotyping of limited number of cases and no really specific karyotypic changes have yet been identified. As the majority of the genes are conserved among mammals, the use of inbred animal model systems may serve as a tool for identification of underlying genes and pathways involved in tumorigenesis in humans. In the present work we used spectral karyotyping (SKY) to identify cancer-related aberrations in a well-characterized experimental model for spontaneous endometrial carcinoma in the BDII rat tumor model. Results: Analysis of 21 experimental ECs revealed specific nonrandom numerical and structural chromosomal changes. The most recurrent numerical alterations were gains in rat chromosome 4 (RNO4) and losses in RNO15. The most commonly structural changes were mainly in form of chromosomal translocations and were detected in RNO3, RNO6, RNO10, RNO11, RNO12, and RNO20. Unbalanced chromosomal translocations involving RNO3p was the most commonly observed structural changes in this material followed by RNO11p and RNO10 translocations. Conclusion: The non-random nature of these events, as documented by their high frequencies of incidence, is suggesting for dynamic selection of these changes during experimental EC tumorigenesis and therefore for their potential contribution into development of this malignancy. Comparative molecular analysis of the identified genetic changes in this tumor model with those reported in the human ECs may provide new insights into underlying genetic changes involved in EC development and tumorigenesis.

  • 76.
    Falck, Eva
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Karlsson, Sandra
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Carlsson, Jessica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Helenius, Gisela
    Örebro University Hospital.
    Karlsson, Mats
    Örebro University Hospital.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma2010In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 10, p. 46-Article in journal (Refereed)
    Abstract [en]

    Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.

  • 77.
    Falck, Eva
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Expression patterns of PHF5A/Phf5a and GJa1/Gja1 in rat and human endometrial cancer2013In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 13, no 1, article id 43Article in journal (Refereed)
    Abstract [en]

    Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.

    A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.

    We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.

    Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.

  • 78.
    Feldhahn, Magdalena
    et al.
    University of Tübingen, Center for Bioinformatics, Applied Bioinformatics, Sand 14, 72076 Tübingen, Germany.
    Dönnes, Pierre
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Schubert, Benjamin
    University of Tübingen, Center for Bioinformatics, Applied Bioinformatics, Sand 14, 72076 Tübingen, Germany.
    Schilbach, Karin
    University Children's Hospital, Department of, Hematology/Oncology, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
    Rammensee, Hans-Georg
    University of Tübingen, Department of Immunology, Auf der Morgenstelle 15, 72076 Tuebingen, Germany.
    Kohlbacher, Oliver
    University of Tübingen, Center for Bioinformatics, Applied Bioinformatics, Sand 14, 72076 Tübingen, Germany / University of Tübingen, Quantitative Biology Center, Tübingen, Germany.
    miHA-Match: Computational detection of tissue-specific minor histocompatibility antigens2012In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 386, no 1-2, p. 94-100Article in journal (Refereed)
    Abstract [en]

    Allogenic stem cell transplantation has shown considerable success in a number of hematological malignancies, in particular in leukemia. The beneficial effect is mediated by donor T cells recognizing patient-specific HLA-binding peptides. These peptides are called minor histocompatibility antigens (miHAs) and are typically caused by single nucleotide polymorphisms. Tissue-specific miHAs have successfully been used in anti-tumor therapy without causing unspecific graft-versus-host reactions. However, only a small number of miHAs have been identified to date, limiting the clinical use.

    Here we present an immunoinformatics pipeline for the identification of miHAs. The pipeline can be applied to large-scale miHA screening, for example, in the development of diagnostic tests. Another interesting application is the design of personalized miHA-based cancer therapies based on patient-donor pair-specific miHAs detected by this pipeline. The suggested method covers various aspects of genetic variant detection, effects of alternative transcripts, and HLA-peptide binding. A comparison of our computational pipeline and experimentally derived datasets shows excellent agreement and coverage of the computationally predicted miHAs.

  • 79.
    Fernandes, Ricardo A.
    et al.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom / Department of Molecular and Cellular Physiology, Department of Structural Biology, Stanford University, United States.
    Ganzinger, Kristina A.
    Department of Chemistry, University of Cambridge, United Kingdom / Living Matter Department, Physics of Cellular Interactions Group, AMOLF, Amsterdam, Netherlands.
    Tzou, Justin C.
    Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, United States.
    Jönsson, Peter
    Department of Chemistry, University of Cambridge, United Kingdom / Department of Chemistry, Lund University, Sweden.
    Lee, Steven F.
    Department of Chemistry, University of Cambridge, United Kingdom.
    Palayret, Matthieu
    Department of Chemistry, University of Cambridge, United Kingdom.
    Santos, Ana Mafalda
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Carr, Alexander R.
    Department of Chemistry, University of Cambridge, United Kingdom.
    Ponjavic, Aleks
    Department of Chemistry, University of Cambridge, United Kingdom.
    Chang, Veronica T.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom / Neurobiology Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
    Macleod, Charlotte
    Department of Chemistry, University of Cambridge, United Kingdom.
    Lagerholm, B. Christoffer
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Lindsay, Alan E.
    Mathematics Department, University of British Columbia, Vancouver, Canada.
    Dushek, Omer
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom / Wolfson Centre for Mathematical Biology, University of Oxford, United Kingdom.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. School of Bioscience, University of Skövde, Sweden.
    Davis, Simon J.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Klenerman, David
    Department of Chemistry, University of Cambridge, United Kingdom.
    A cell topography-based mechanism for ligand discrimination by the T cell receptor2019In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, no 28, p. 14002-14010Article in journal (Refereed)
    Abstract [en]

    The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes. 

  • 80.
    Fioretto, Paola
    et al.
    Department of Medicine, University of Padova, Padova, Italy.
    Del Prato, Stefano
    Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy.
    Buse, John B.
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Goldenberg, Ronald
    LMC Diabetes & Endocrinology, Thornhill, Canada.
    Giorgino, Francesco
    Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy.
    Reyner, Daniel
    AstraZeneca, Gaithersburg, Maryland, USA.
    Langkilde, Anna Maria
    AstraZeneca, Gothenburg, Sweden.
    Sjöstrom, C. David
    AstraZeneca, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca, Gothenburg, Sweden.
    Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study2018In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, no 11, p. 2532-2540Article in journal (Refereed)
    Abstract [en]

    Aims: Dapagliflozin is a selective inhibitor of sodium glucose co-transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45-59 mL/min/1.73 m(2); chronic kidney disease [CKD] stage 3A). Materials and methods: In this double-blind, parallel group, Phase 3 study (NCT02413398, ) patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N = 160) or matching placebo (N = 161) for 24 weeks. Randomization was stratified by pre-enrolment glucose-lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24. Results: At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], -0.34% [-0.53, -0.15]; P < 0.001), body weight (difference [95% CI], -1.25 kg [-1.90, -0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], -0.9 mmol/L [-1.5, -0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], -3.1 mmHg [-6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (-2.49 mL/min/1.73 m(2) [-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61 mL/min/1.73 m(2) [-1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported. Conclusions: The findings of this study (NCT02413398, ) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.

  • 81.
    Fransson, S.
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Uv, A.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Eriksson, H.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden.
    Andersson, M. K.
    Department of Pathology, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
    Wettergren, Y.
    Department of General Surgery, University of Gothenburg SE-40530 Gothenburg, Sweden.
    Bergo, M.
    Department of Medicine, Sahlgrenska Cancer Center, University of Gothenburg, SE-40530 Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors2012In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 31, no 27, p. 3277-3286Article in journal (Refereed)
    Abstract [en]

    The phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, proliferation and survival, and are frequently affected in human cancer. PI3K is composed of a catalytic subunit, p110, and a regulatory subunit, p85. The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain. Here we present an alternatively spliced PIK3CD transcript encoding a previously unknown protein, p37δ, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37δ retains the p85-binding domain and a fraction of the RAS-binding domain, lacks the catalytic domain, and has a unique carboxyl-terminal region. In contrast to p110δ, which stabilizes p85, p37δ promoted p85 sequestering. Despite the truncated RAS-binding domain, p37δ bound to RAS and we found a strong positive correlation between the protein levels of p37δ and RAS. Overexpressing p37δ, but not p110δ, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37δ showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37δ in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37δ appears to be a new tumor-specific isoform of p110δ with growth-promoting properties.

  • 82.
    Fransson, Susanne
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Abel, Frida
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Kogner, Per
    Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Martinsson, Tommy
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Stage-dependent expression of PI3K/Akt‑pathway genes in neuroblastoma2013In: International Journal of Oncology, ISSN 1019-6439, Vol. 42, no 2, p. 609-616Article in journal (Refereed)
    Abstract [en]

    The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival and has also been implicated in the development of the childhood cancer neuroblastoma. In neuroblastoma high mRNA expression of the PI3K catalytic isoform PIK3CD is associated to favorable disease. Yet, activation of Akt is associated with poor prognosis. Since the contribution of the numerous members of this pathway to neuroblastoma pathogenesis is mainly unknown, genes of the PI3K/Akt pathway were analyzed at the mRNA level through microarrays and quantitative real-time RT-PCR (TaqMan) and at the protein level using western blot analysis. Five genes showed lower mRNA expression in aggressive compared to more favorable neuroblastomas (PRKCZ, PRKCB1, EIF4EBP1, PIK3RI and PIK3CD) while the opposite was seen for PDGFRA. Clustering analysis shows that the expression levels of these six genes can predict aggressive disease. At the protein level, p110δ (encoded by PIK3CD) and p85α isomers (encoded by PIK3R1) were more highly expressed in favorable compared to aggressive neuroblastoma. Evaluation of the expression of these PI3K genes can predict aggressive disease, and indicates stage-dependent involvement of PI3K-pathway members in neuroblastoma.

  • 83.
    Fransson, Susanne
    et al.
    Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
    High level of p37δ-mRNA relative to p110δ-mRNA in neuroblastoma tumors correlates with poor patient survival2013In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 4, article id 724Article in journal (Refereed)
    Abstract [en]

    Alterations in the PI3K/Akt pathway, a pathway that promotes proliferation and oncogenic transformation, are common in various cancers. In neuroblastoma, activation of Akt is correlated with aggressive disease although mutations in genes of this pathway are rare. Previous findings include a few mutations in PIK3CD, the gene encoding PI3K catalytic subunit delta, p110delta. We recently reported that an alternatively spliced form of p110delta, called p37delta, had cell proliferative properties and was over-expressed in ovarian and colorectal tumors. Here, we investigated p37delta in neuroblastoma primary tumors of different stages using qPCR (TaqMan) for gene expression analysis (46 samples) and Western blot for protein analysis (22 samples). Elevated levels of both p37delta-mRNA and p110delta-mRNA were detected in metastasizing neuroblastoma tumors compared to normal adrenal gland (P<0.05), and higher expression of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma non-survivor patients compared to survivors (P<0.01). p37delta-Protein levels but not p110delta levels correlated with increased pAKT(T308) and pERK levels. The p37delta-mRNA levels did not correlate with the protein levels, indicating major regulation at the translational/protein level. Deregulation of signaling pathways is a hallmark of cancer development. Here, we show that p37delta, a kinase-dead isoform of the PI3K catalytic subunit p110delta, is over-expressed in neuroblastoma tumors, and that it correlates with the activation of both PI3K/Akt- and RAS-signaling pathways.

  • 84.
    Fransson, Susanne
    et al.
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Kogner, Per
    Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institutet, Stockholm, Sweden.
    Martinsson, Tommy
    Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ejeskär, Katarina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Aggressive neuroblastomas have high p110alpha but low p110delta and p55alpha/p50alpha protein levels compared to low stage neuroblastomas2013In: Journal of Molecular Signaling, ISSN 1750-2187, E-ISSN 1750-2187, Vol. 8, no 1, article id 4Article in journal (Refereed)
    Abstract [en]

    Background: The phosphoinositide 3-kinase (PI3K)/Akt pathway is involved in neuroblastoma development where Akt/PKB activation is associated with poor prognosis. PI3K activity subsequently activates Akt/PKB, and as mutations of PI3K are rare in neuroblastoma and high levels of PI3K subunit p110delta is associated with favorable disease with low p-Akt/PKB, the levels of other PI3K subunits could be important for Akt activation.Methods: Protein levels of Type IA PI3K catalytic and regulatory subunits were investigated together with levels of phosphorylated Akt/PKB and the PI3K negative regulator PTEN in primary neuroblastoma tumors. Relation between clinical markers and protein levels were evaluated through t-tests. Results: We found high levels of p-Akt/PKB correlating to aggressive disease and p-Akt/PKB (T308) showed inverse correlation to PTEN levels. The regulatory isomers p55alpha/p50alpha showed higher levels in favorable neuroblastoma as compared with aggressive neuroblastoma. The PI3K-subunit p110alpha was found mainly in advanced tumors while p110delta showed higher levels in favorable neuroblastoma.Conclusions: Activation of the PI3K/Akt pathway is seen in neuroblastoma tumors, however the contribution of the different PI3K isoforms is unknown. Here we show that p110alpha is preferentially expressed in aggressive neuroblastomas, with high p-Akt/PKB and p110delta is mainly detected in favorable neuroblastomas, with low p-Akt/PKB. This is an important finding as PI3K-specific inhibitors are suggested for enrollment in treatment of neuroblastoma patients. © 2013 Fransson et al.; licensee BioMed Central Ltd.

  • 85.
    Frisk, Mikael
    et al.
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Jonsson, Annie
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Sellman, Stefan
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Flisberg, Patrik
    The Forestry Research Institute of Sweden, Uppsala, Sweden.
    Rönnqvist, Mikael
    Département de génie mécanique, Université Laval, Québec, Canada.
    Wennergren, Uno
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 3, article id e0193223Article in journal (Refereed)
    Abstract [en]

    Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact.

  • 86.
    Fröberg, L.
    et al.
    Botanical Museum, Lund, Sweden.
    Niklasson, M.
    Institute of Southern Swedish Forest Research Centre, Alnarp, Sweden.
    Paltto, Heidi
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Ecology, Swedish Agricultural University, Uppsala, Sweden.
    Knutsson, T.
    Nedre Västerstad 111, Mörbylånga, Sweden.
    Johansson, T.
    County Administrator of Kalmar, Kalmar, Sweden.
    Age and epiphytic lichen diversity of the dwarf shrub Helianthemum oelandicum on the island of Öland , Sweden2009In: The Lichenologist, ISSN 0024-2829, E-ISSN 1096-1135, Vol. 41, no 5, p. 537-545Article in journal (Refereed)
    Abstract [en]

    Lichen cover and diversity was analysed on the dwarf shrub Helianthemum oelandicum (L.) Dum.Cours.at one site in the calcareous grassland of the area known as the 'Great Alvar' on the Island of Öland, Sweden. The age of 22 phorophytes was determined by ring counting and varied from 8 to 41 years and was accurately predicted by the root diameter. A total of 18 lichen species were found, with a range between 0 and 13 species per phorophyte. The number of lichen species on living H. oelandicum was correlated with the phorophyte age. The number of lichen species and their coverage was greater on dead compared with living phorophytes. The species number was also higher on thin branches compared with thick branches and roots and some of the species showed preferences for dead phorophytes, and for thin branches. This study of lichen colonization and growth on dwarf shrubs in relation to phorophyte age is a new application of herbchronology.

  • 87.
    Frössling, Jenny
    et al.
    Department of Disease Control and Epidemiology, National Veterinary Institute, Uppsala, Sweden / Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Ohlson, Anna
    Department of Disease Control and Epidemiology, National Veterinary Institute, Uppsala, Sweden / Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Björkman, Camilla
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Håkansson, Nina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Division of Theoretical Biology, IFM Theory and Modelling, Linköping University, Linköping, Sweden.
    Nöremark, Maria
    Department of Disease Control and Epidemiology, National Veterinary Institute, Uppsala, Sweden.
    Application of network analysis parameters in risk-based surveillance - Examples based on cattle trade data and bovine infections in Sweden2012In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 105, no 3, p. 202-208Article in journal (Refereed)
    Abstract [en]

    Financial resources may limit the number of samples that can be collected and analysed in disease surveillance programmes. When the aim of surveillance is disease detection and identification of case herds, a risk-based approach can increase the sensitivity of the surveillance system. In this paper, the association between two network analysis measures, i.e. ‘in-degree’ and ‘ingoing infection chain’, and signs of infection is investigated. It is shown that based on regression analysis of combined data from a recent cross-sectional study for endemic viral infections and network analysis of animal movements, a positive serological result for bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) is significantly associated with the purchase of animals. For BCV, this association was significant also when accounting for herd size and regional cattle density, but not for BRSV. Examples are given for different approaches to include cattle movement data in risk-based surveillance by selecting herds based on network analysis measures. Results show that compared to completely random sampling these approaches increase the number of detected positives, both for BCV and BRSV in our study population. It is concluded that network measures for the relevant time period based on updated databases of animal movements can provide a simple and straight forward tool for risk-based sampling.

  • 88.
    Gamalielsson, Jonas
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Developing Semantic Pathway Comparison Methods for Systems Biology2009Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Systems biology is an emerging multi-disciplinary field in which the behaviour of complex biological systems is studied by considering the interaction of many cellular and molecular constituents rather than using a “traditional” reductionist approach where constituents are studied individually. Systems are often studied over time with the ultimate goal of developing models which can be used to understand and predict complex biological processes, such as human diseases. To support systems biology, a large number of biological pathways are being derived for many different organisms, and these are stored in various databases. This pathway collection presents an opportunity to compare and contrast pathways, and to utilise the knowledge they represent. This thesis presents some of the first algorithms that are designed to explore this opportunity. It is argued that the methods will be useful to biologists in order to assess the biological plausibility of derived pathways, compare different biological pathways for semantic similarities, and to derive putative pathways that are semantically similar to documented biological pathways. The methods will therefore extend the systems biology toolbox that biologists can use to make new biological discoveries.

  • 89.
    Gamalielsson, Jonas
    et al.
    University of Skövde, School of Humanities and Informatics.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Gene Ontology-based Semantic Alignment of Biological Pathways by Evolutionary Search2008In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 6, no 4, p. 825-842Article in journal (Refereed)
    Abstract [en]

    A large number of biological pathways have been elucidated recently, and there is a need for methods to analyze these pathways. One class of methods compares pathways semantically in order to discover parts that are evolutionarily conserved between species or to discover intraspecies similarities. Such methods usually require that the topologies of the pathways being compared are known, i.e. that a query pathway is being aligned to a model pathway. However, sometimes the query only consists of an unordered set of gene products. Previous methods for mapping sets of gene products onto known pathways have not been based on semantic comparison of gene products using ontologies or other abstraction hierarchies. Therefore, we here propose an approach that uses a similarity function defined in Gene Ontology (GO) terms to find semantic alignments when comparing paths in biological pathways where the nodes are gene products. A known pathway graph is used as a model, and an evolutionary algorithm (EA) is used to evolve putative paths from a set of experimentally determined gene products. The method uses a measure of GO term similarity to calculate a match score between gene products, and the fitness value of each candidate path alignment is derived from these match scores. A statistical test is used to assess the significance of evolved alignments. The performance of the method has been tested using regulatory pathways for S. cerevisiae and M. musculus.

  • 90.
    Gamalielsson, Jonas
    et al.
    University of Skövde, School of Humanities and Informatics.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Humanities and Informatics.
    On the (lack of) robustness of gene expression data clustering2004In: WSEAS Transactions on Biology and Biomedicine, ISSN 1109-9518, E-ISSN 2224-2902, Vol. 1, no 2, p. 198-204Article in journal (Refereed)
    Abstract [en]

    We assess the robustness of partitional clustering algorithms applied to gene expression data. A number of clusterings are made with identical parameter settings and input data using SOM and  k-means algorithms, which both rely on random initialisation and may produce different clusterings with different seeds. We define a reproducibility index and use it to assess the algorithms. The index is based on the number of pairs of genes consistently clustered together in different clusterings. The effect of noise applied to the original data is also studied. Our results show a lack of robustness for both classes of algorithms, with slightly higher reproducibility for SOM than for k-means.

  • 91.
    Gao, Jingfang
    et al.
    Department of Oncology, Institute of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden.
    Zhang, Hong
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Arbman, Gunnar
    Department of Surgery, Östergötland, Sweden.
    Sun, Xiao-Feng
    Department of Oncology, Institute of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden.
    RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, no 12, p. 1495-1502Article in journal (Refereed)
    Abstract [en]

    RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity. In this study, we immunohistochemically examined MRE11, NBS1 and RAD50 expression in primary CRCs (n = 208), the corresponding distant (n= 41) and adjacent normal mucosa ( n= 130), and lymph node metastases ( n= 26), and investigated their clinicopathological significance in colorectal cancers ( CRCs). We found that the intensity and percentage of MRE11 and NBS1 in primary CRCs were positively correlated with each other and with RAD50 (P < 0.0001). Strong expression of MRE11, NBS1 or combined RAD50/MRE11/NBS1 was related to MSS, positive hMLH1 expression, earlier tumour stage (TNM stage I and II) and favourable survival (P < 0.05). A high percentage of MRE11 expression was associated with less local recurrence and high apoptotic activity (P < 0.05). In MSS CRCs, the expression of MRE11 and NBS1 was stronger than that in normal mucosa (P < 0.05), and strong expression of NBS1 in primary tumour was related to favourable survival of patients in TNM stage I and II (univariate analysis: P = 0.03; multivariate analysis: P = 0.07). In MSI CRCs, neither MRE11 nor NBS1 expression showed differences among normal mucosa, primary tumour and metastasis, or among clinicopathological variables. In conclusion, RAD50/MRE11/NBS1 proteins interacted with each other, which had different clinicopathological significance in MSS and MSI CRCs, and further, each component of the complex might have additional roles. NBS1 might be a prognostic factor for patients with MSS tumour in TNM stage I and II.

  • 92.
    Garcia, Danilo
    et al.
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden.
    Persson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Network for Empowerment and Well-Being, Sweden / Department of Psychology, University of Turku, Finland.
    Al Nima, Ali
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Network for Empowerment and Well-Being, Sweden.
    Gruneau Brulin, Joel
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Rapp-Ricciardia, Max
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden.
    Kajonius, Petri J.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden / Department of Behavioral Sciences, University West, Sweden.
    IRT analyses of the Swedish Dark Triad Dirty Dozen2018In: Heliyon, ISSN 2405-8440, Vol. 4, no 3, article id e00569Article in journal (Refereed)
  • 93.
    Gerafi, Joel
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Long-term functional outcome after ischemic stroke: Prognostic value of early identification of neglect and aphasia2017Licentiate thesis, comprehensive summary (Other academic)
  • 94.
    Gerafi, Joel
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / The Skaraborg Institute for Research and Development, Skövde, Sweden.
    Samuelsson, H.
    Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Viken, J. I.
    Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blomgren, C.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Claesson, L.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Kallio, Sakari
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jern, C.
    Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blomstrand, C.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Jood, K.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Neurology, The Sahlgrenska University Hospital, Gothenburg, Sweden.
    Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 11, p. 1407-1415Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Visuospatial inattention (VSI) and languageimpairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. Methods: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1–5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian StrokeScale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. Results: The regression model significantly explained variance in the modified Rankin scale (R2= 0.435, P < 0.001) and identified VSI (P=0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for FrenchayActivities Index was also significant (R2= 0.269, P < 0.001) with VSI(P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. Conclusions: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

  • 95.
    Ghosal, Anubrata
    et al.
    University of Copenhagen.
    Humayan Kabir, Ahmad
    Flinders University.
    Mandal, Abul
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    RNA interference and its therapeutic potential2011In: Central European Journal of Medicine, ISSN 1895-1058, E-ISSN 1644-3640, Vol. 6, no 2, p. 137-147Article, review/survey (Refereed)
    Abstract [en]

    RNA interference is a technique that has become popular in the past few years. This is a biological method to detect the activity of a specific gene within a cell. RNAi is the introduction of homologous double stranded RNA to specifically target a gene’s product resulting in null or hypomorphic phenotypes. This technique involves the degradation of specific mRNA by using small interfering RNA. Both microRNA (miRNA) and small interfering RNA (siRNA) are directly related to RNA interference. RNAi mechanism is being explored as a new technique for suppressing gene expression. It is an important issue in the treatment of various diseases. This review considers different aspects of RNAi technique including its history of discovery, molecular mechanism, gene expression study, advantages of this technique against previously used techniques, barrier associated with this technique, and its therapeutic application.

  • 96.
    Ghosheh, Nidal
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Asplund, Annika
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Edsbagge, Josefina
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, Tommy B.
    Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Björquist, Petter
    NovaHep Aktiebolaget, Gothenburg, Sweden.
    Andersson, Christian X.
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca Research and Development, Global Medicines Development Cardiovascular and Metabolic Diseases Global Medicines Development Unit, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue2017In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 49, no 8, p. 430-446Article in journal (Refereed)
    Abstract [en]

    Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte differentiation. Using functional annotation, pathway and protein interaction network analyses, we observed the grouping of differentially expressed genes in specific clusters representing typical developmental stages of hepatic differentiation. In addition, we identified hub proteins and modules that were involved in the cell cycle process at early differentiation stages. We also identified hub proteins that differed in expression levels between hPSC-HEP and the liver tissue controls. Moreover, we identified a module of genes that were expressed at higher levels in the liver tissue samples than in the hPSC-HEP. Considering that hub proteins and modules generally are essential and have important roles in the protein-protein interactions, further investigation of these genes and their regulators may contribute to a better understanding of the differentiation process. This may suggest novel target pathways and molecules for improvement of hPSC-HEP functionality, having the potential to finally bring this technology to a wider use.

  • 97.
    Ghosheh, Nidal
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Edsbagge, Josefina
    Takara Bio Europe AB, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe AB, Gothenburg, Sweden.
    Van Giezen, Mariska
    Takara Bio Europe AB, Gothenburg, Sweden.
    Asplund, Annika
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, Tommy B.
    AstraZeneca R&D, CVMD DMPK, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Björquist, Petter
    NovaHep AB, Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca R&D, GMD CVMD GMed, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines2016In: Stem Cells International, ISSN 1687-9678, Vol. 2016, article id 8648356Article in journal (Refereed)
    Abstract [en]

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

  • 98.
    Gnosa, Sebastian
    et al.
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Shen, Yang-Mei
    Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
    Wang, Chao-Jie
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Zhang, Hong
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Stratmann, Johannes
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sun, Xiao-Feng
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden / Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden.
    Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines2012In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 10, article id 109Article in journal (Refereed)
    Abstract [en]

    Background: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. Material and methods: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. Results: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/- 0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p < 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-kappa B, p73, Rad50 and apoptosis (p < 0.05). Conclusion: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-kappa B signaling pathway.

  • 99.
    Godoy, Patricio
    et al.
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany / Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile.
    Schmidt-Heck, Wolfgang
    Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, Jena, Germany.
    Natarajan, Karthick
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Lucendo-Villarin, Baltasar
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Szkolnicka, Dagmara
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Asplund, Annika
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
    Björquist, Petter
    NovaHep AB, Gothenburg, Sweden.
    Widera, Agata
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Stöber, Regina
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Campos, Gisela
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Hammad, Seddik
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Sachinidis, Agapios
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Chaudhari, Umesh
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Damm, Georg
    Charité University Medicine Berlin, Department of General-, Visceral- and Transplantation Surgery, Berlin, Germany.
    Weiss, Thomas S.
    Center for Liver Cell Research, Department of Pediatrics and Juvenile Medicine, University of Regensburg Hospital, Regensburg, Germany.
    Nüssler, Andreas
    Eberhard Karls University Tübingen, BG Trauma Center, Siegfried Weller Institut, Tübingen, Germany.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Edlund, Karolina
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Küppers-Munther, Barbara
    Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
    Hay, David C.
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Hengstler, Jan G.
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells2015In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 63, no 4, p. 934-942Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.

    METHODS: Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.

    RESULTS: Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The "unwanted" intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.

    CONCLUSIONS: The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation.

  • 100.
    Grankvist, Gunne
    et al.
    Department of Social and Behavioural Studies, University West, Trollhättan, Sweden.
    Kajonius, Petri
    Department of Social and Behavioural Studies, University West, Trollhättan, Sweden.
    Persson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    The Relationship between Mind-Body Dualism and Personal Values2016In: International Journal of Psychological Studies, ISSN 1918-7211, E-ISSN 1918-722X, Vol. 8, no 2, p. 126-132Article in journal (Refereed)
    Abstract [en]

    Dualists view the mind and the body as two fundamental different “things”, equally real and independent of each other. Cartesian thought, or substance dualism, maintains that the mind and body are two different substances, the non-physical and the physical, and a causal relationship is assumed to exist between them. Physicalism, on the other hand, is the idea that everything that exists is either physical or totally dependent of and determined by physical items. Hence, all mental states are fundamentally physical states. In the current study we investigated to what degree Swedish university students’ beliefs in mind-body dualism is explained by the importance they attach to personal values. A self-report inventory was used to measure their beliefs and values. Students who held stronger dualistic beliefs attach less importance to the power value (i.e., the effort to achieve social status, prestige, and control or dominance over people and resources). This finding shows that the strength in laypeople’s beliefs in dualism is partially explained by the importance they attach to personal values

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