his.sePublications
Change search
Refine search result
2345678 201 - 250 of 474
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 201.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Probabilistic network modelling of the impact of penicillin consumption on spread of pneumococci2011In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 139, no 9, p. 1351-1360Article in journal (Refereed)
    Abstract [en]

    The worldwide increase of resistant S. pneumoniae is a growing clinical problem. In several countries, a more restrictive use of penicillin has been promoted in hope of slowing the rates of resistant pneumococci. However, the consequences of such an action on pneumococcal population dynamics are not fully understood. Thus, a network model was constructed to assess the impacts of penicillin consumption and between-strain competition on the spread of penicillin non-susceptible pneumococci. Model simulations suggest that the age distribution for carriage of penicillin non-susceptible pneumococci, in contrast to susceptible pneumococci, is affected by penicillin consumption. Furthermore, it appears extremely difficult to reduce the incidence of penicillin non-susceptible pneumococci by simply controlling penicillin consumption, assuming that reduced penicillin susceptibility does not confer a fitness cost for the organism. A more judicious use of penicillin together with control measures are in that case required to manage penicillin resistance in pneumococci.

  • 202.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Streptococcus pneumoniae is one of the major contributors to mortality and morbidity around  the  world.  It  causes  a  wide  variety  of  diseases  ranging  from  uncomplicated respiratory  infections  to  life-threatening  invasive  infections  such  as  meningitis  and septicemia. In recent years, the effectiveness of antibiotic therapy has been hampered by  the  increasing  rates  of  resistant  pneumococci.  As  antibiotic  resistance  increases, there is a growing need for interventions that minimize opportunities for development and spread  of resistant  pneumococci.  The aim  of this  thesis  was  to learn  more  about emergence  and  spread  of  antibiotic  resistant  pneumococci  using  both  theoretical  and empirical methods.  Since the increasing prevalence of resistant pneumococci is mainly due to the spread of strains belonging to few clones, interventions for controlling pneumococcal transmission  in  the  community  were  studied.  Model  predictions  suggested  that interventions for efficiently control organism transmission should include reduction of group sizes in the day-care centers. Simulations also indicated that it appears extremely difficult  to  reduce  the  rates  of  penicillin  non-susceptible  pneumococci  by  simply decreasing  the  penicillin  consumption  assumed  that  reduced  penicillin  susceptibility does not imply a fitness cost for the organism. Managing the penicillin resistance rates in pneumococci then probably requires a more restrictive use of penicillin together with other  control  measures  such  as  vaccine  programs.  Although  clonal  spread  is  the primary  mechanism  for  the  rapid  emergence  of  resistance  in  pneumococci,  natural competence  for  genetic  transformation  also  seems  to  be  involved.  Further  molecular understanding  of competence regulation  is  important  to be  able  to prevent  horizontal spread  of  resistance  genes.  Studying  the  competence  regulation  by  theoretical  means led  to  the  conclusion  that  down-regulation  of  competence  is  probably  caused  by  a repressor acting on the comCDE operon at the level of transcription.  Despite the globally emerging frequency of resistant pneumococci, we conclude in a prospective study that antimicrobial resistance in invasive pneumococci in south-west Sweden remains limited. Any correlations between resistance pattern and clinical parameters could not be revealed. However, the serotype distribution was observed to differ  between  strains  with  reduced  susceptibility  and  fully  susceptible  strains  as isolates  with  decreased  susceptibility  more  frequently  belonged  to  the  serotypes included in the 7-valent vaccine.

  • 203.
    Karlsson, Diana
    et al.
    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.
    Ljungström, Lars
    Department of Infectious Diseases- Skaraborg Hospital, Skövde, Sweden.
    Multimarker approach for sepsis diagnostics2015In: 25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015, European Society of ClinicalMicrobiology and Infectious Diseases (ESCMID) , 2015Conference paper (Refereed)
    Abstract [en]

    OBJECTIVES

    The aim of this study was to assess the performance of a multimarker model in distinguishing patients with sepsis from those with non-infective systemic inflammatory response.

    METHODS

    This study is part of a prospective study of community-onset severe sepsis and septic shock in adults conducted from September 2011 to June 2012 at Skaraborg Hospital, in the western region of Sweden. The levels of 92 inflammation-related human protein biomarkers were measured simultaneously using Proseek® Multiplex Inflammation I96x96 (Olink Bioscience, Sweden) in 122 plasma samples collected from patients suspected with sepsis. After pre-processing normalization procedure, measurements of the markers were obtained as Normalized Protein eXpression (NPX) units on a log2 scale (GenEx, MultiD Analyses AB, Sweden). The study was approved by the Regional Ethical Review Board of Gothenburg (376-11). All patients enrolled provided written informed consent.

    To reduce the number of markers, factor analysis was performed. Thereafter, a multimarker model for classification was derived using discriminant analysis. The multimarker model consisted of a linear function of the selected markers. Cross-validation was performed by classifying each sample by the discriminant function derived from all samples other than that specific sample. The performance was assessed as area under receiving operating characteristic (ROC) curve. The cut-off for sensitivity and specificity was derived from the cut score of the discriminant function. Statistical analyses were performed in SPSS 22.0 (IBM Corporation Somers, NY USA).

    RESULTS

    Of the 122 samples, 80 (66%) were from patients diagnosed with sepsis and 42 from patients with non-infective systemic inflammatory response syndrome (SIRS). The five markers selected for the multimarker model were interleukin-6 (IL-6), cystatin D (CST5), delta and notch-like epidermal growth factor-related receptor (DNER), STAM-binding protein (STAMPB), macrophage colony-stimulating factor 1 (CSF 1). Every single marker was statistically different between the groups (p value < 0.001), except for DNER (p value 0.064) and STAMPB (p value 0.060). The area under ROC was higher for the multimarker model (81%) than for each biomarker separately (Figure 1). The accuracy for the multimarker model was 72% [64-80, 95% CI]; sensitivity 84% [77-91, 95% CI]; specificity 60% [51-69, 95% CI]; positive predictive value 79% [72-86, 95% CI]; and negative predictive value 66% [58-74, 95% CI].

    CONCLUSION

    A higher power of discrimination is obtained by combining more than one biomarker. However, the multimarker candidates identified in this study need further assessment.

  • 204.
    Karlsson, Patrik
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Jonsson, Tomas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Jonsson, Annie
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Food web structure and interaction strength pave the way for vulnerability to extinction2007In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 249, no 1, p. 77-92Article in journal (Refereed)
    Abstract [en]

    This paper focuses on how food web structure and interactions among species affects the vulnerability, due to environmental variability, to extinction of species at different positions in model food webs. Vulnerability is here not measured by a traditional extinction threshold but is instead inspired by the IUCN criteria for endangered species: an observed rapid decline in population abundance. Using model webs influenced by stochasticity with zero autocorrelation, we investigate the ecological determinants of species vulnerability, i.e. the trophic interactions between species and food web structure and how these interact with the risk of sudden drops in abundance of species. We find that (i) producers fulfil the criterion of vulnerable species more frequently than other species, (ii) food web structure is related to vulnerability, and (iii) the vulnerability of species is greater when involved in a strong trophic interaction than when not. We note that our result on the relationship between extinction risk and trophic position of species contradict previous suggestions and argue that the main reason for the discrepancy probably is due to the fact that we study the vulnerability to environmental stochasticity and not extinction risk due to overexploitation, habitat destruction or interactions with introduced species. Thus, we suggest that the vulnerability of species to environmental stochasticity may be differently related to trophic position than the vulnerability of species to other factors.

    Earlier research on species extinctions has looked for intrinsic traits of species that correlate with increased vulnerability to extinction. However, to fully understand the extinction process we must also consider that species interactions may affect vulnerability and that not all extinctions are the result of long, gradual reductions in species abundances. Under environmental stochasticity (which importance frequently is assumed to increase as a result of climate change) and direct and indirect interactions with other species some extinctions may occur rapidly and apparently unexpectedly. To identify the first declines of population abundances that may escalate and lead to extinctions as early as possible, we need to recognize which species are at greatest risk of entering such dangerous routes and under what circumstances. This new perspective may contribute to our understanding of the processes leading to extinction of populations and eventually species. This is especially urgent in the light of the current biodiversity crisis where a large fraction of the world's biodiversity is threatened.

  • 205.
    Karlsson, Sandra
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Gene Expression Patterns in a Rat Model of Human Endometrial Adenocarcinoma2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Endometrial cancer develops from the endometrium of the uterus and is the most common pelvic malignancy diagnosed in women in the western society. Similar to all cancer diseases, endometrial cancer is a disorder that results from complex patterns of genetic and epigenetic alterations involved in the malignant transformation. The BDII/Han rat model is unique for spontaneous hormonal carcinogenesis since more than 90% of the female virgins spontaneously develop endometrial cancer. The possibility to perform global gene expression profiling of tumor cells would likely provide important information of the genes and pathways that are aberrant in endometrial adenocarcinoma (EAC). The works in the present thesis have been focused on investigating the expression patterns in endometrial tumors.  The findings in this thesis involve the identification of a novel candidate tumor suppressor region of rat chromosome 10. This genomic segment contains 18 potential tumor suppressor genes. Preliminary microarray data analysis confirmed that this region might contain relevant candidate genes as the EACs on average had 3.8 times lower expression of Crk in comparison to the normal/premalignant endometrial tissue cultures. Furthermore, an expression analysis using qPCR, revealed a significant down-regulation of Myo1c and Hic.   We were also able to identify a group of genes associated with the TGF-Beta pathway that were differentially expressed between endometrial tumors and normal/pre-malignant endometrium. These results suggest that the TGF-Beta signaling pathway is disrupted in EAC. This has previously been demonstrated in human EAC, although this is the first report on aberrant expression of TGF-Beta downstream target genes.  Evaluation of Gpx3 down-regulation in the rat EAC cell lines revealed an almost complete loss of expression in a majority of the endometrial tumors. From methylation studies, we could conclude that the loss of expression of Gpx3 is correlated with biallelic hypermethylation in the Gpx3 promoter region. This result was confirmed with a demethylation study of EAC cell lines, where the Gpx3 mRNA expression was restored after treatment with a demethylation agent and a deacetylation inhibitor. We also showed that mRNA expression of the well-known oncogene, Met, was slightly higher in endometrial tumors with loss of Gpx3 expression. A likely consequence of loss of Gpx3 function is a higher amount of reactive oxygen species (ROS) in the cancer cell environment. Since it has been proposed that overproduction of ROS is required for the hypoxic activation of HIF-1, we suggest that loss of Gpx3 expression activates transcription of Met through induction of the transcription factor HIF-1. The loss of the protective properties of GPX3 most likely makes the endometrial cells more vulnerable to ROS damage and genome instability.  We extended the results obtained from the rat endometrial tumors to human material, and conducted expression analysis of GPX3 in 30 endometrial human tumors using qPCR. The results showed a uniformly down-regulation of GPX3 in 29 of the tumors, independent of tumor grade. We thus concluded that the down-regulation of GPX3 probably occurs at an early stage of EAC and therefore contributes to the EAC carcinogenesis. These results suggest that there are important clinical implications of GPX3 expression in EAC, both as a biomarker for EAC and as a potential target for therapeutics.

     

  • 206.
    Karlsson, Sandra
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Olausson, Josefin
    University of Skövde, School of Life Sciences.
    Lundh, Dan
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Sögård, Peter
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Holmström, Kjell-Ove
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Stahel, Anette
    University of Skövde, School of Life Sciences.
    Bengtsson, Jenny
    University of Skövde, School of Life Sciences.
    Larsson, Dennis
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Vitamin D and prostate cancer: The role of membrane initiated signaling pathways in prostate cancer progression2010In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 121, no 1-2, p. 413-416Article in journal (Refereed)
    Abstract [en]

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been demonstrated to mediate both genomic and non-genomic responses in prostate cancer (CaP) cells. Here, we give an overview of membrane initiated 1,25(OH)2D3 signaling in prostate cancer cell progression. The presence of PDIA3 was investigated and homologous modeling of the putative PDIA3 receptor complex was conducted. Furthermore, the cellular distribution of nVDR was analyzed. We could show that both nVDR and PDIA3 are expressed in the prostate cancer cell lines investigated. The homologous modeling of PDIA3 showed that the receptor complex exists in a trimer formation, which suggests for allosteric activity. Our findings support previous reports and suggest that 1,25(OH)2D3 is an important therapeutic agent in inhibiting prostate cancer progression. Furthermore, our data show that 1,25(OH)2D3 regulate prostate cell biology via multiple pathways and targeting specific pathways for 1,25(OH)2D3 might provide more effective therapies compared to the vitamin D therapies currently clinically tested.

  • 207.
    Karlsson, Sandra
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Klinga-Levan, Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model2009In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 9, p. Article Number: 12-Article in journal (Refereed)
    Abstract [en]

     

    Background: In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Initial symptoms are often vague and may be confused with several other conditions or disorders. Thus, there is a need for an easy and reliable diagnostic tool. The objective of this work was to identify a gene expression signature specific for endometrial adenocarcinomas to be used for testing potential endometrial biomarkers.

    Results: Changes in expression between endometrial adenocarcinomas and non-/pre-malignant endometrium from the BDII EAC rat model were compared in cDNA microarray assays. By employing classification analysis (Weka) on the expression data from approximately 5600 cDNA clones and TDT analysis on genotype data, we identified a three-gene signature (Gpx3, Bgn and Tgfb3). An independent analysis of differential expression, revealed a total of 354 cDNA clones with significant changes in expression. Among the 10 best ranked clones, Gpx3, Bgn and Tgfb3 were found.

     

    Conclusion: Taken together, we present a unique data set of genes with different expression patterns between EACs and non-/pre-malignant endometrium, and specifically we found three genes that were confirmed in two independent analyses. These three genes are candidates for an EAC signature and further evaluations of their involvement in EAC tumorigenesis will be undertaken.

  • 208.
    Karpushevskaia, Anastasiia
    et al.
    AtlantNIRO, Kaliningrad, Russian Federation.
    Nielsen, Anders
    DTU Aqua - National Institute of Aquatic Resources, Charlottenlund, Denmark.
    Mikhaylov, Andrey
    Atlantic Research Institute of Fisheries and Oceanography (AtlantNIRO), Moscow, Russian Federation.
    Luzenczyk, Anna
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Florin, Ann-Britt
    Swedish University of Agricultural Sciences Institute of Coastal Research, Öregrund, Sweden.
    Albert, Anu
    Estonian Marine Institute, University of Tartu, Tartu, Estonia.
    Berg, Casper Willestofte
    DTU Aqua National Institute of Aquatic Resources, Section for Fisheries Advice, Charlottenlund, Denmark.
    Ustups, Didzis
    Institute of Food Safety Animal Health and Environment (BIOR), Fish Resources Research Department, Riga, Latvia.
    Svecovs, Fausts
    Institute of Food Safety Animal Health and Environment (BIOR), Fish Resources Research Department, Riga, Latvia.
    Bastardie, François
    DTU Aqua, National Institute of Aquatic Resources, Charlottenlund, Denmark.
    Kornilovs, Georgs
    Institute of Food Safety Animal Health and Environment (BIOR), Fish Resources Research Department, Riga, Latvia.
    Strods, Guntars
    Institute of Food Safety Animal Health and Environment (BIOR), Fish Resources Research Department, Riga, Latvia.
    Strehlow, Harry Vincent
    Thünen Institute, Baltic Sea Fisheries, Rostock, Germany.
    Degel, Henrik
    DTU Aqua, National Institute of Aquatic Resources, Section for Monitoring and Data, Charlottenlund, Denmark.
    Karpushevskiy, Igor
    AtlantNIRO, Kaliningrad, Russian Federation.
    Sics, Ivo
    Institute of Food Safety Animal Health and Environment (BIOR), Fish Resources Research Department, Riga, Latvia.
    Horbowy, Jan
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Raitaniemi, Jari
    Natural Resources Institute Finland, Turku, Finland.
    Boje, Jesper
    DTU Aqua, Arctic Section, Charlottenlund, Denmark.
    Hjelm, Joakim
    Swedish University of Agricultural Sciences, Institute of Marine Research, Lysekil, Sweden.
    Lövgren, Johan
    Swedish University of Agricultural Sciences, Institute of Marine Research, Lysekil, Sweden.
    Pönni, Jukka
    Natural Resources Institute Finland, Natural resources and bioproduction, Helsinki, Finland.
    Hommik, Kristiina
    Estonian Marine Institute, University of Tartu, Tartu, Estonia.
    Öhman, Kristin
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Lysekil, Sweden.
    Radtke, Krzysztof
    National Marine Fisheries, Research Institute, Gdynia, Poland.
    Eero, Margit
    DTU Aqua, National Institute of Aquatic Resources, Charlottenlund, Denmark.
    Storr-Paulsen, Marie
    DTU Aqua, National Institute of Aquatic Resources, Section for Fisheries Advice, Charlottenlund, Denmark.
    Plikshs, Maris
    Institute of Food Safety Animal Health and Environment (BIOR), Riga, Latvia.
    Pedersen, Martin Wæver
    DTU Aqua, National Institute of Aquatic Resources, Charlottenlund, Denmark.
    Casini, Michele
    Swedish University of Agricultural Sciences, Institute of Marine Research, Lysekil, Sweden.
    Bergenius, Mikaela
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Lysekil, Sweden.
    Holmgren, Noél
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kaljuste, Olavi
    Swedish University of Agricultural Sciences, Institute of Coastal Research, Öregrund, Sweden.
    Afanasyev, Pavel
    Atlantic Research Institute of Fisheries and Oceanography (AtlantNIRO), Moscow, Russian Federation.
    Gasyukov, Pavel
    AtlantNIRO, Kaliningrad, Russian Federation.
    Jounela, Pekka
    Natural Resources Institute Finland, Statistical methods, Turku Finland.
    Oeberst, Rainer
    Thünen Institute, Baltic Sea Fisheries, Rostock, Germany.
    Statkus, Romas
    Fisheries Service under the Ministry of Agriculture, Division of Fisheries Research and Science, Klaipeda, Lithuania.
    Carlshamre, Sofia
    Swedish University of Agricultural Sciences, Institute of Marine Research, Lysekil, Sweden.
    Jonusas, Stanislovas
    European Commission Directorate for Maritime Affairs and Fisheries, Brussels, Belgium.
    Neuenfeldt, Stefan
    DTU Aqua, National Institute of Aquatic Resources, Section for Fisheries Advice Population Ecology and Genetics, Charlottenlund, Denmark.
    Stoetera, Sven
    Thünen Institute Baltic Sea Fisheries, Rostock, Germany.
    Smolinski, Szymon
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Raid, Tiit
    Estonian Marine Institute University of Tartu, Tallinn, Estonia.
    Arula, Timo
    Estonian Marine Institute, University of Tartu, Dept. of Ecodynamics, Lootsiza, Estonia.
    Gröhsler, Tomas
    Thünen Institute Baltic Sea Fisheries, Rostock, Germany.
    Zolubas, Tomas
    Fisheries Service under the Ministry of Agriculture, Vilnius, Lithuania.
    Krumme, Uwe
    Thünen Institute Baltic Sea Fisheries, Rostock, Germany.
    Amosova, Viktoriia
    AtlantNIRO, Kaliningrad, Russian Federation.
    Grygiel, Wlodzimierz
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Pekcan-Hekim, Zeynep
    Swedish University of Agricultural Sciences, Institute of Coastal Research, Öregrund, Sweden.
    Mirny, Zuzanna
    National Marine Fisheries Research Institute, Gdynia, Poland.
    Report of the Baltic Fisheries Assessment Working Group (WGBFAS), 12-19 April 2016, ICES HQ, Copenhagen, Denmark2016Report (Refereed)
  • 209.
    Kazemi, Ali
    et al.
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Kajonius, Petri
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Variations in user-oriented elderly care: a multilevel approach2017In: International Journal of Quality and Service Sciences, ISSN 1756-669X, E-ISSN 1756-6703, Vol. 9, no 2, p. 138-147Article in journal (Refereed)
  • 210.
    Kazemi, Ali
    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.
    Cost and satisfaction trends in Swedish elderly home care2016In: Home Health Care Management & Practice, ISSN 1084-8223, E-ISSN 1552-6739, Vol. 28, no 4, p. 250-255Article in journal (Refereed)
  • 211.
    Kia, Richard
    et al.
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England.
    Kelly, Lorna
    Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England.
    Sison-Young, Rowena L. C.
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England.
    Zhang, Fang
    Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England.
    Pridgeon, Chris S.
    Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England.
    Heslop, James A.
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England.
    Metcalfe, Pete
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England.
    Kitteringham, Neil R.
    Univ Liverpool, Dept Mol & Clin Pharmacol, England / Stem Cells Safer Med, London, England.
    Baxter, Melissa
    Univ Manchester, Fac Life Sci, Manchester, England / Univ Cent Lancashire, Sch Med & Dent, Preston, England.
    Harrison, Sean
    Stem Cells Safer Med, London, England / Acad Hlth Sci Ctr, Fac Med & Human Sci, Ctr Endocrinol & Diabet,Inst Human Dev, Manchester, England.
    Hanley, Neil A.
    Stem Cells Safer Med, London, England / Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Med & Human Sci, Ctr Endocrinol & Diabet,Inst Human Dev, Manchester, England / Cent Manchester Univ Hosp NHS Fdn Trust, Endocrinol Dept, Manchester England.
    Burke, Zoe D.
    Stem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England.
    Storm,, Mike P.
    Stem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England.
    Welham, Melanie J.
    Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England.
    Tosh, David
    Stem Cells Safer Med, London, England / Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath, England.
    Küppers-Munther, Barbara
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Takara Bio Europe AB, Gothenburg, Sweden.
    Edsbagge, Josefina
    Takara Bio Europe AB, Gothenburg, Sweden.
    Lewis, Philip J. Starkey
    Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland.
    Bonner, Frank
    Stem Cells Safer Med, London, England.
    Harpur, Ernie
    Stem Cells Safer Med, London, England / Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
    Sidaway, James
    Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland / AstraZeneca R&D, Drug Safety & Metab, Cheshire, England.
    Bowes, Joanne
    Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland / AstraZeneca R&D, Drug Safety & Metab, Cheshire, England.
    Fenwick, Stephen W.
    Aintree Univ Hosp NHS Fdn Trust, North Western Hepatobiliary Unit, Liverpool, England.
    Malik, Hassan
    Aintree Univ Hosp NHS Fdn Trust, North Western Hepatobiliary Unit, Liverpool, England.
    Goldring, Chris E. P.
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England / Stem Cells Safer Med, London England.
    Park, B. Kevin
    Univ Liverpool, Dept Mol & Clin Pharmacol, MRC Ctr Drug Safety Sci, Liverpool, England / Stem Cells Safer Med, London, England.
    MicroRNA-122: a novel hepatocyte-enriched in vitro marker of drug-induced cellular toxicity2015In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 144, no 1, p. 173-185Article in journal (Refereed)
    Abstract [en]

    Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.

  • 212.
    Koivisto, Mika
    et al.
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Grassini, Simone
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Hurme, Mikko
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Salminen-Vaparanta, Niina
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Vorobyev, Victor
    Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    Tallus, Jussi
    Department of Radiology, Turku University Hospital, Turun yliopisto, Finland.
    Paavilainen, Teemu
    Department of Radiology, Turku University Hospital, Turun yliopisto, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Turun yliopisto, Finland / Centre for Cognitive Neuroscience, University of Turku, Turun yliopisto, Finland.
    TMS-EEG reveals hemispheric asymmetries in top-down influences of posterior intraparietal cortex on behavior and visual event-related potentials2017In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 107, p. 94-101Article in journal (Refereed)
    Abstract [en]

    Clinical data and behavioral studies using transcranial magnetic stimulation (TMS) suggest right-hemisphere dominance for top-down modulation of visual processing in humans. We used concurrent TMS-EEG to directly test for hemispheric differences in causal influences of the right and left intraparietal cortex on visual event-related potentials (ERPs). We stimulated the left and right posterior part of intraparietal sulcus (IPS1) while the participants were viewing and rating the visibility of bilaterally presented Gabor patches. Subjective visibility ratings showed that TMS of right IPS shifted the visibility toward the right hemifield, while TMS of left IPS did not have any behavioral effect. TMS of right IPS, but not left one, reduced the amplitude of posterior N1 potential, 180–220 ms after stimulus-onset. The attenuation of N1 occurred bilaterally over the posterior areas of both hemispheres. Consistent with previous TMS-fMRI studies, this finding suggests that the right IPS has top-down control on the neural processing in visual cortex. As N1 most probably reflects reactivation of early visual areas, the current findings support the view that the posterior parietal cortex in the right hemisphere amplifies recurrent interactions in ventral visual areas during the time-window that is critical for conscious perception.

  • 213.
    Koivisto, Mika
    et al.
    University of Turku, Turku, Finland.
    Grassini, Simone
    University of Turku, Turku, Finland.
    Salminen-Vaparanta, Niina
    University of Turku, Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Turku, Finland.
    Different Electrophysiological Correlates of Visual Awareness for Detection and Identification2017In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, no 9, p. 1621-1631Article in journal (Refereed)
    Abstract [en]

    Detecting the presence of an object is a different process than identifying the object as a particular object. This difference has not been taken into account in designing experiments on the neural correlates of consciousness. We compared the electrophysiological correlates of conscious detection and identification directly by measuring ERPs while participants performed either a task only requiring the conscious detection of the stimulus or a higher-level task requiring its conscious identification. Behavioral results showed that, even if the stimulus was consciously detected, it was not necessarily identified. A posterior electrophysiological signature 200-300 msec after stimulus onset was sensitive for conscious detection but not for conscious identification, which correlated with a later widespread activity. Thus, we found behavioral and neural evidence for elementary visual experiences, which are not yet enriched with higher-level knowledge. The search for the mechanisms of consciousness should focus on the early elementary phenomenal experiences to avoid the confounding effects of higher-level processes.

  • 214.
    Koivisto, Mika
    et al.
    University of Turku, Finland.
    Kastrati, Granit
    University of Skövde.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Recurrent processing enhances visual awareness but is not necessary for fast categorization of natural scenes2014In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 26, no 2, p. 223-231Article in journal (Refereed)
    Abstract [en]

    Humans are rapid in categorizing natural scenes. Electrophysiological recordings reveal that scenes containing animals can be categorized within 150 msec, which has been interpreted to indicate that feedforward flow of information from V1 to higher visual areas is sufficient for visual categorization. However, recent studies suggest that recurrent interactions between higher and lower levels in the visual hierarchy may also be involved in categorization. To clarify the role of recurrent processing in scene categorization, we recorded EEG and manipulated recurrent processing with object substitution masking while the participants performed a go/no-go animal/nonanimal categorization task. The quality of visual awareness was measured with a perceptual awareness scale after each trial. Masking reduced the clarity of perceptual awareness, slowed down categorization speed for scenes that were not clearly perceived, and reduced the electrophysiological difference elicited by animal and nonanimal scenes after 150 msec. The results imply that recurrent processes enhance the resolution of conscious representations and thus support categorization of stimuli that are difficult to categorize on the basis of the coarse feedforward representations alone.

  • 215.
    Koivisto, Mika
    et al.
    University of Turku, Finland.
    Kirjanen, Svetlana
    University of Helsinki, Finland.
    Revonsuo, Antti
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Kallio, Sakari
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    A Preconscious Neural Mechanism of Hypnotically Altered Colors: A Double Case Study2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, article id e70900Article in journal (Refereed)
    Abstract [en]

    Hypnotic suggestions may change the perceived color of objects. Given that chromatic stimulus information is processed rapidly and automatically by the visual system, how can hypnotic suggestions affect perceived colors in a seemingly immediate fashion? We studied the mechanisms of such color alterations by measuring electroencephalography in two highly suggestible participants as they perceived briefly presented visual shapes under posthypnotic color alternation suggestions such as "all the squares are blue''. One participant consistently reported seeing the suggested colors. Her reports correlated with enhanced evoked upper beta-band activity (22 Hz) 70-120 ms after stimulus in response to the shapes mentioned in the suggestion. This effect was not observed in a control condition where the participants merely tried to simulate the effects of the suggestion on behavior. The second participant neither reported color alterations nor showed the evoked beta activity, although her subjective experience and event-related potentials were changed by the suggestions. The results indicate a preconscious mechanism that first compares early visual input with a memory representation of the suggestion and consequently triggers the color alteration process in response to the objects specified by the suggestion. Conscious color experience is not purely the result of bottom-up processing but it can be modulated, at least in some individuals, by top-down factors such as hypnotic suggestions.

  • 216.
    Koivisto, Mika
    et al.
    Department of Psychology, University of Turku, Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Turku, Finland.
    Salminen-Vaparanta, Niina
    Department of Psychology, University of Turku, Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Turku, Finland.
    Grassini, Simone
    Department of Psychology, University of Turku, Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Turku, Finland.
    Subjective visual awareness emerges prior to P32016In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 43, no 12, p. 1601-1611Article in journal (Refereed)
    Abstract [en]

    Studies on the neural basis of visual awareness, the subjective experience of seeing, have found several potential neural corre- lates of visual awareness. Some of them may not directly correlate with awareness but with post-perceptual processes, such as reporting one’s awareness of the stimulus. We dissociated potential electrophysiological correlates of visual awareness from those occurring during response selection and thus co-occurring with post-perceptual processing. The participants performed two GO-NOGO conditions. In the aware-GO condition they responded with a key press when they were aware of the stimulus and withheld responding when they were unaware of it. In the unaware-GO condition they withheld responding when they were aware and responded when they were not aware of the stimulus. Thus, event-related potentials could be measured to aware and una- ware trials when responding was required and when not required. The results revealed that the N200 amplitude (180–280 ms) over the occipital and posterior temporal cortex was enhanced in aware trials as compared with trials without awareness. This effect (visual awareness negativity, VAN) did not depend on responding. The amplitude of P3 (350–450 ms) also was enhanced in aware trials as compared with unaware trials. In addition, the amplitudes in the P3 time window depended on responding: they were greater when awareness was mapped to GO-response than when not, suggesting that P3 reflects post-perceptual process- ing, that is, it occurs after awareness has emerged. These findings support theories of visual awareness that assume a relatively early onset of visual awareness before P3. 

  • 217.
    Kotta, Jonne
    et al.
    Estonian Marine Institute, University of Tartu, Tallinn, Estonia.
    Vanhatalo, Jarno
    Department of Mathematics and Statistics and Organismal and Evolutionary Biology Research Program, University of Helsinki, Helsinki, Finland.
    Jänes, Holger
    Estonian Marine Institute, University of Tartu, Tallinn, Estonia / Centre for Integrative Ecology, Deakin University, Melbourne, Victoria, Australia.
    Orav-Kotta, Helen
    Estonian Marine Institute, University of Tartu, Tallinn, Estonia.
    Rugiu, Luca
    Department of Biology, University of Turku, Turku, Finland.
    Jormalainen, Veijo
    Department of Biology, University of Turku, Turku, Finland.
    Bobsien, Ivo
    GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.
    Viitasalo, Markku
    Finnish Environment Institute, Helsinki, Finland.
    Virtanen, Elina
    Finnish Environment Institute, Helsinki, Finland.
    Nyström Sandman, Antonia
    AquaBiota Water Research, Stockholm, Sweden.
    Isaeus, Martin
    AquaBiota Water Research, Stockholm, Sweden.
    Leidenberger, Sonja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jonsson, Per R.
    Department of Marine Sciences – Tjärnö, University of Gothenburg, Tjärnö, Strömstad, Sweden.
    Johannesson, Kerstin
    Department of Marine Sciences – Tjärnö, University of Gothenburg, Tjärnö, Strömstad, Sweden.
    Integrating experimental and distribution data to predict future species patterns2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1821Article in journal (Refereed)
    Abstract [en]

    Predictive species distribution models are mostly based on statistical dependence between environmental and distributional data and therefore may fail to account for physiological limits and biological interactions that are fundamental when modelling species distributions under future climate conditions. Here, we developed a state-of-the-art method integrating biological theory with survey and experimental data in a way that allows us to explicitly model both physical tolerance limits of species and inherent natural variability in regional conditions and thereby improve the reliability of species distribution predictions under future climate conditions. By using a macroalga-herbivore association (Fucus vesiculosus - Idotea balthica) as a case study, we illustrated how salinity reduction and temperature increase under future climate conditions may significantly reduce the occurrence and biomass of these important coastal species. Moreover, we showed that the reduction of herbivore occurrence is linked to reduction of their host macroalgae. Spatial predictive modelling and experimental biology have been traditionally seen as separate fields but stronger interlinkages between these disciplines can improve species distribution projections under climate change. Experiments enable qualitative prior knowledge to be defined and identify cause-effect relationships, and thereby better foresee alterations in ecosystem structure and functioning under future climate conditions that are not necessarily seen in projections based on non-causal statistical relationships alone.

  • 218.
    Kristensson, Lisbeth
    et al.
    AstraZeneca, Mölndal, Sweden.
    Lundin, Anders
    AstraZeneca, Mölndal, Sweden / Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, David
    Emeriti Bio, AZ Bioventure Hub, Mölndal, Sweden.
    Fryklund, Jan
    Emeriti Bio, AZ Bioventure Hub, Mölndal, Sweden.
    Fex, Tomas
    Emeriti Bio, AZ Bioventure Hub, Mölndal, Sweden.
    Delsing, Louise
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca, Mölndal, Sweden / the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Ryberg, Erik
    AstraZeneca, Mölndal, Sweden.
    Plasminogen binding inhibitors demonstrate unwanted activities on GABAA and glycine receptors in human iPSC derived neurons2018In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 681, p. 37-43, article id S0304-3940(18)30351-3Article in journal (Refereed)
    Abstract [en]

    Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABAA and glycine receptors. These cells respond to GABA (EC50 0.33 ± 0.18 μM), glycine (EC50 11.0 ± 3.7 μM) and additional ligands in line with previous reports from patch clamp technologies. Additionally, we identify and characterize a competitive antagonistic behavior of the prototype inhibitor and drug tranexamic acid (TXA). Finally, we demonstrate proof of concept for effective counter-screening of lead series compounds towards unwanted GABAAreceptor activities. No activity was observed for a previously identified PBI candidate drug, AZD6564, whereas a discontinued analog, AZ13267257, could be characterized as a potent GABAA receptor agonist.

  • 219.
    Kunze, Angelika
    et al.
    Department of Applied Physics, Chalmers University of Technology, Göteborg, Sweden / Institute of Physical Chemistry, University of Göttingen, Göttingen, Germany.
    Steel, Daniella
    Cellectis AB, Göteborg, Sweden / Abcam, Cambridge, United Kingdom.
    Dahlenborg, Kerstin
    Cellectis AB, Göteborg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Cellectis AB, Göteborg, Sweden / AstraZeneca R&D, Mölndal, Sweden.
    Svedhem, Sofia
    Department of Applied Physics, Chalmers University of Technology, Göteborg, Sweden.
    Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile Machinery of Human Cardiomyocyte Clusters2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, p. 1-10, article id e0125540Article in journal (Refereed)
    Abstract [en]

    There is an urgent need for improved models for cardiotoxicity testing. Here we propose acoustic sensing applied to beating human cardiomyocyte clusters for non-invasive, surrogate measuring of the QT interval and other characteristics of the contractile machinery. In experiments with the acoustic method quartz crystal microbalance with dissipation monitoring (QCM-D), the shape of the recorded signals was very similar to the extracellular field potential detected in electrochemical experiments, and the expected changes of the QT interval in response to addition of conventional drugs (E-4031 or nifedipine) were observed. Additionally, changes in the dissipation signal upon addition of cytochalasin D were in good agreement with the known, corresponding shortening of the contraction-relaxation time. These findings suggest that QCM-D has great potential as a tool for cardiotoxicological screening, where effects of compounds on the cardiomyocyte contractile machinery can be detected independently of whether the extracellular field potential is altered or not.

  • 220.
    Küppers-Munther, Barbara
    et al.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Asplund, A.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    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.
    Abadie, A.
    Takara Bio Europe SAS, Paris, France.
    Novel human iPSC-derived hepatocytes with advanced functionality and long-term 2D cultures of human primary hepatocytes for metabolic disease studies2018In: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 29, no 12, p. A146-A146, article id P406Article in journal (Refereed)
  • 221.
    Laaksonen, L.
    et al.
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland.
    Kallioinen, M.
    Turku University Hospital, Turku, Finland.
    Långsjö, J.
    Tampere University Hospital, Tampere, Finland.
    Laitio, T.
    Turku University Hospital, Turku, Finland.
    Scheinin, A.
    University of Turku. Turku, Finland / Turku University Hospital, Turku, Finland.
    Scheinin, J.
    Kuopio University Hospital, Kuopio, Finland.
    Kaisti, K.
    Oulu University Hospital, Oulu, Finland.
    Maksimow, A.
    Turku University Hospital, Turku, Finland.
    Kallionpää, R. E.
    Turku University Hospital, Turku, Finland / University of Turku, Turku, Finland.
    Rajala, V.
    Turku University Hospital, Turku, Finland.
    Johansson, J.
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland / Umeå University, Umeå, Sweden.
    Kantonen, O.
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland / University of California, Irvine, CA, USA.
    Nyman, M.
    Turku University Hospital, Turku, Finland.
    Sirén, S.
    Turku University Hospital, Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Turku University Hospital, Turku, Finland / University of Turku, Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Turku, Finland.
    Solin, O.
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland.
    Vahlberg, T.
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland.
    Alkire, M.
    University of California, Irvine, CA, USA.
    Scheinin, Harry
    University of Turku, Turku, Finland / Turku University Hospital, Turku, Finland.
    Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study2018In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 121, no 1, p. 281-290Article in journal (Refereed)
    Abstract [en]

    IntroductionThe highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses.

    MethodsOne hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml−1n=40), propofol (1.7 μg ml−1n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 μg ml−1n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions.

    ResultsAt the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRgludid not differ from placebo.

    ConclusionsAt equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia.

  • 222.
    Larsson, Dennis
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Jonas, Adele
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Bergsten, Niklas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Ståhl, Fredrik
    University College of Borås, School of Health Sciences, Sweden.
    Karlsson, Sandra
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Membrane Initiated Effects of1α,25-Dihydroxyvitamin D3 inProstate Cancer Cells: Effects on AP1 and CREB Mediated Transcription2012In: Current Frontiers and Perspectives in Cell Biology / [ed] Stevo Najman, InTech, 2012, p. 153-162Chapter in book (Refereed)
  • 223.
    Laurio, Kim
    et al.
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Svensson, Thomas
    Biovitrum AB, Göteborg, Sweden.
    Jirstrand, Mats
    Fraunhofer-Chalmers Research Center for Industrial Mathematics, Göteborg, Sweden.
    Nilsson, Patric
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Gamalielsson, Jonas
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Evolutionary search for improved path diagrams2007In: Evolutionary Computation, Machine Learning and Data Mining in Bioinformatics: 5th European Conference, EvoBIO 2007, Valencia, Spain, April 11-13, 2007. Proceedings / [ed] Elena Marchiori, Jason H. Moore, Jagath C. Rajapakse, Springer Berlin/Heidelberg, 2007, p. 114-121Conference paper (Refereed)
    Abstract [en]

    A path diagram relates observed, pairwise, variable correlations to a functional structure which describes the hypothesized causal relations between the variables. Here we combine path diagrams, heuristics and evolutionary search into a system which seeks to improve existing gene regulatory models. Our evaluation shows that once a correct model has been identified it receives a lower prediction error compared to incorrect models, indicating the overall feasibility of this approach. However, with smaller samples the observed correlations gradually become more misleading, and the evolutionary search increasingly converges on suboptimal models. Future work will incorporate publicly available sources of experimentally verified biological facts to computationally suggest model modifications which might improve the model’s fitness.

  • 224.
    Leidenberger, Sonja
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Boström, Sven
    Swedish Museum Nat Hist, Dept Zool, Stockholm, Sweden.
    Wayland, Matthew T.
    Univ Cambridge, Dept Zool, England.
    Morphological observations on three Baltic species of Corynosoma Lühe, 1905 (Acanthocephala, Polymorphidae)2019In: European Journal of Taxonomy, ISSN 2118-9773, Vol. 514, p. 1-19Article in journal (Refereed)
    Abstract [en]

    Necropsies of Baltic grey (Halichoerus grypus) and ringed seals (Pusa hispida) presented a rare opportunity to study their acanthocephalan fauna. Both species hosted adults of three species of the genus Corynosoma Lithe, 1904, namely C. magdaleni Montreuil, 1958, C. semerme (Forsell, 1904) Lithe 1911 and C. strumosum (Rudolphi, 1802) Lithe 1904. A comparative morphological analysis of these three species of Corynosoma, combining both light and scanning electron microscopy, was performed for the first time. Sexual dimorphism in the size and shape of the trunk was observed in both C. magdaleni and C. semerme, but there was insufficient material to investigate this phenomenon in C. strumosum. Genital spines were not observed in any of the female acanthocephalans. Three possible explanations for the presence of genital spines in some females, but not others are (i) cryptic speciation, (ii) phenotypic variation and (iii) loss by extraction or shearing when the copulatory cap is released. Copulatory caps were observed on female C. semerme. The size and morphology showed considerable variability and all caps were strongly autofluoresecent.

  • 225.
    Lennartsson, Jenny
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Networks and epidemics - impact of network structure on disease transmission2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The spread of infectious diseases, between animals as well as between humans, is a topic often in focus. Outbreaks of diseases like for example foot-and-mouth disease, avian influenza, and swine influenza have in the last decades led to an increasing interest in modelling of infectious diseases since such models can be used to elucidate disease transmission and to evaluate the impact of different control strategies. Different kind of modelling techniques can be used, e.g. individual based disease modelling, Bayesian analysis, Markov Chain Monte Carlo simulations, and network analysis. The topic in this thesis is network analysis, since this is a useful method when studying spread of infectious diseases. The usefulness lies in the fact that a network describes potential transmission routes, and to have knowledge about the structure of them is valuable in predicting the spread of diseases. This thesis contains both a method for generating a wide range of different theoretical networks, and also examination and discussion about the usefulness of network analysis as a tool for analysing transmission of infectious animal diseases between farms in a spatial context. In addition to the theoretical networks, Swedish animal transport networks are used as empirical examples.

    To be able to answer questions about the effect of the proportion of contacts in networks, the effect of missing links and about the usefulness of network measures, there was a need to manage to generate networks with a wide range of different structures. Therefore, it was necessary to develop a network generating algorithm. Papers I and II describes that network generating algorithm, SpecNet, which creates spatial networks. The aim was to develop an algorithm that managed to generate a wide range of network structures. The performance of the algorithm was evaluated by some network measures. In the first study, Paper I, the algorithm succeeded to generate a wide range of most of the investigated network measures. Paper II is an improvement of the algorithm to produce networks with low negative assortativity by adding two classes of nodes instead of one. Except to generate theoretical networks from scratch, it is also relevant that a network generating algorithm has the potential to regenerate a network with given specific structures. Therefore, we tested to regenerate two Swedish animal transport networks according to their structures. SpecNet managed to mimic the two empirical networks well in comparison with a non-spatial network generating algorithm that was not equally successful in regenerating the requested structures.

    Sampled empirical networks are rarely complete, since contacts are often missing during sampling, e.g. due to difficulties to sample or due to too short time window during sampling. In Paper III, the focus is on the effect on disease transmission, due to number of contacts in the network, as well as on the reliability of making predictions from networks with a small proportion of missing links. In addition, attention is also given to the spatial distribution of animal holdings in the landscape and on what effect this distribution has on the resulting disease transmission between the holdings. Our results indicate that, assuming weighted contacts, it is maybe risky to make predictions about disease transmission from one single network replicate with as low proportion of contacts as in most empirical animal transport networks.

    In case of a disease outbreak, it would be valuable to use network measures as predictors for the progress and the extent of the disease transmission. Then a reliable network is required, and also that the used network measures has the potential to make reasonable predictions about the epidemic. In Paper IV we investigate if network measures are useful as predictors for eventual disease transmissions. Moreover, we also analyse if there is some measure that correlates better with disease transmission than others. Disease transmission simulations are performed in networks with different structures to mimic diverse spatial conditions, thereafter are the simulation results compared to the values of the network structures.

  • 226.
    Lennartsson, Jenny
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Håkansson, Nina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Physics and Measurement Technology, Biology and Chemistry, Theory and Modelling, Linköping University, Linköping, Sweden.
    Wennergren, Uno
    Department of Physics and Measurement Technology, Biology and Chemistry, Theory and Modelling, Linköping University, Linköping, Sweden.
    Jonsson, Annie
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    SpecNet: A Spatial Network Algorithm that Generates a Wide Range of Specific Structures2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 8, article id e42679Article in journal (Refereed)
    Abstract [en]

    Network measures are used to predict the behavior of different systems. To be able to investigate how various structures behave and interact we need a wide range of theoretical networks to explore. Both spatial and non-spatial methods exist for generating networks but they are limited in the ability of producing wide range of network structures. We extend an earlier version of a spatial spectral network algorithm to generate a large variety of networks across almost all the theoretical spectra of the following network measures: average clustering coefficient, degree assortativity, fragmentation index, and mean degree. We compare this extended spatial spectral network-generating algorithm with a non-spatial algorithm regarding their ability to create networks with different structures and network measures. The spatial spectral networkgenerating algorithm can generate networks over a much broader scale than the non-spatial and other known network algorithms. To exemplify the ability to regenerate real networks, we regenerate networks with structures similar to two real Swedish swine transport networks. Results show that the spatial algorithm is an appropriate model with correlation coefficients at 0.99. This novel algorithm can even create negative assortativity and managed to achieve assortativity values that spans over almost the entire theoretical range.

  • 227.
    Levan, Kristina
    et al.
    University of Gothenburg.
    Partheen, Karolina
    University of Gothenburg.
    Österberg, Lovisa
    University of Gothenburg.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Delle, Ulla
    University of Gothenburg.
    Eklind, Saskia
    University of Gothenburg.
    Horvath, György
    University of Gothenburg.
    Identification of a Gene Expression Signature for Survival Prediction in Type I Endometrial Carcinoma2010In: Gene Expression, ISSN 1052-2166, E-ISSN 1555-3884, Vol. 14, no 6, p. 361-370Article in journal (Refereed)
    Abstract [en]

    Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.

  • 228.
    Lewander, Andreas
    et al.
    Department of Oncology, Institute of Clinical and Experimental Medicine, University of Linköping, SE-581 85 Linköping, Sweden.
    Gao, Jinfang
    Department of Oncology, Institute of Clinical and Experimental Medicine, University of Linköping, SE-581 85 Linköping, Sweden.
    Adell, Gunnar
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Zhang, Hong
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Sun, Xiao-Feng
    Department of Oncology, Institute of Clinical and Experimental Medicine, University of Linköping, SE-581 85 Linköping, Sweden.
    Expression of NF-kappa B p65 phosphorylated at serine-536 in rectal cancer with or without preoperative radiotherapy2011In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 45, no 4, p. 279-284Article in journal (Refereed)
    Abstract [en]

    Background. In the present study, we investigated NF-kappa B p65 phosphorylated at Serine-536 (phosphor-Ser536-p65) in rectal cancer and its relationship to preoperative radiotherapy (RT), clinicopathological variables and biological factors. Patients and methods. Expression of phosphor-Ser536-p65 was examined by using immunohistochemistry in 141 primary rectal cancers, 149 normal mucosa specimens and 48 metastases in the lymph nodes, from rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. Results. The expression of phosphor-Ser536-p65 in the cytoplasm increased from normal mucosa to primary tumour (p<0.0001, for both the group that did and the group that did not received RT). The expression did not further increase from primary tumour to metastasis in either group (p>0.05). Expression of phosphor-Ser536-p65 was positively related to, or tended to be related to, the expression of tumour endothelium marker 1 (TEM1, p=0.02), FXYD-3 (p=0.001), phosphatase of regenerating liver (PRL, p=0.02), p73 (p=0.048) and meningioma associated protein (MAC30, p=0.05) in the group that received RT but there were no such relationships in the group that did not received RT (p>0.05). The expression of phosphor-Ser536-p65 was not related to clinicopathological factors including survival (p>0.05). Conclusions. The increased expression of phosphor-Ser536-p65 may be involved in rectal cancer development. After RT, phosphor-Ser536-p65 seems to be positively related to the biological factors, which associated with more malignant features of tumours. However, phosphor-Ser536-p65 was not directly related to the response of RT based on recurrence and survival.

  • 229.
    Li, Kaitao
    et al.
    Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, USA.
    Cheng, Xiaoxiao
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Davis, Simon J.
    Radcliffe Department of Medicine and Medical Research Council Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
    Zhu, Cheng
    Coulter Department of Biomedical Engineering, Woodruff School of Mechanical Engineering, Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA.
    In situ and in silico kinetic analyses of programmed cell death-1 (PD-1) receptor, programmed cell death ligands, and B7-1 protein interaction network2017In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 292, no 16, p. 6799-6809Article in journal (Refereed)
    Abstract [en]

    Programmed cell death-1 (PD-1) is an inhibitory receptor with an essential role in maintaining peripheral tolerance and is among the most promising immunotherapeutic targets for treating cancer, autoimmunity, and infectious diseases. A complete understanding of the consequences of PD-1 engagement by its ligands, PD-L1 and PD-L2, and of PD-L1 binding to B7-1 requires quantitative analysis of their interactions at the cell surface. We present here the first complete in situ kinetic analysis of the PD-1/PD-ligands/B7-1 system. Consistent with previous solution measurements, we observed higher in situ affinities for human (h) than murine (m) PD-1 interactions, stronger binding of hPD-1 to hPD-L2 than hPD-L1, and comparable binding of mPD-1 to both ligands. However, in contrast to the relatively weak solution affinities, the in situ affinities of PD-1 are as high as those of the T cell receptor for agonist pMHC and of LFA-1 (lymphocyte function-associated antigen 1) for ICAM-1 (intercellular adhesion molecule 1) but significantly lower than that of the B7-1/CTLA-4 interaction, suggesting a distinct basis for PD-1- versus CTLA-4-mediated inhibition. Notably, the in situ interactions of PD-1 are much stronger than that of B7-1 with PD-L1. Overall, the in situ affinity ranking greatly depends on the on-rate instead of the off-rate. In silico simulations predict that PD-1/PD-L1 interactions dominate at interfaces between activated T cells and mature dendritic cells and that these interactions will be highly sensitive to the dynamics of PD-L1 and PD-L2 expression. Our results provide a kinetic framework for better understanding inhibitory PD-1 activity in health and disease.

  • 230.
    Linde, Jörg
    et al.
    Leibniz-Institute for Natural Product Research and Infection Biology.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lubovac, Zelmina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Network Properties for Ranking Predicted miRNA Targets in Breast Cancer2009In: Advances in Bioinformatics, ISSN 1687-8027, E-ISSN 1687-8035, p. Article ID 182689-Article in journal (Refereed)
    Abstract [en]

    MicroRNAs control the expression of their target genes by translational repression and transcriptional cleavage. They are involved in various biological processes including development and progression of cancer. To uncover the biological role of miRNAs it is important to identify their target genes. The small number of experimentally validated target genes makes computer prediction methods very important. However, state-of-the-art prediction tools result in a great number of putative targets with an unpredictable number of false positives. In this paper, we propose and evaluate two approaches for ranking the biological relevance of putative targets of miRNAs which are associated with breast cancer.

  • 231.
    Lindlöf, Angelica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    In the quest for a cold tolerant variety: gene expression profile analysis of cold stressed oat and rice2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cold acclimation is a process which increases the freezing tolerance of an organism, after exposure to low, non-freezing temperatures. The acclimation ensures that cold tolerant species can endure harsh winter conditions, by preparing them to sub-zero temperatures. Cold-sensitive plants such as oat and rice have limited abilities to cold acclimate and are therefore easily damaged during winter time.

     

    The development of more tolerant varieties by using biotechnological methods is desirable, since the yields are expected to improve due to a prolonged vegetation period. However, in order to apply such methods, more knowledge about the underlying mechanisms regulating the cold tolerance and acclimation is required. One step in this direction is to analyze gene expression data generated from cold stressed oat (Part I) and rice plants (Part II).

     

    The focus of this thesis is, consequently, analysis of expression profiling data, which was generated using the EST sequencing and cDNA microarray technologies. The results show that both oat and rice are cold responsive,with many of the previously identified cold regulated genes having a counterpart in these species. In rice, however, the response is less dynamic than in the model organism Arabidopsis thaliana and this may explain its inability to fully cold acclimate.

     

     

     

    Additionally, the work in this thesis focuses on evaluating if small-scale EST sets can be used for ‘digital-Northern’, in order to identify genes that are involved in the regulation of the cold stress response. The results show that small-scaled EST sets are not optimal for such an analysis, since the method detected only a portion of cold responsive genes represented in the sets. This has to due with the inherent properties of EST data and limitations in the analysis steps of the sequences.

     

    The work also concerns the identification of cis-elements coupled to transcription factors prominent in the regulation of the response. Since cold acclimation is a quantitative trait the response and regulation of cold stress is under combinatorial control of several transcription factors and the results show that this should be taken into account when identifying binding sites.

  • 232.
    Lindlöf, Angelica
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Interplay between low-temperature pathways and light reduction2010In: Plant Signalling & Behavior, ISSN 1559-2316, E-ISSN 1559-2324, Vol. 5, no 7, p. 820-825Article, review/survey (Refereed)
    Abstract [en]

    Low  temperature  is  one  of  the  major  factors  that  adversely affect  crop  yields  by  causing  restraints  on  plant  growth  and productivity.   However,   most   temperate   plants   have   the ability  to  acclimate  to  cooler  temperatures.  Cold  acclimation is  a  process  which  increases  the  freezing  tolerance  of  an organism  after  exposure  to  low,  non-freezing  temperatures. The main trigger is a decrease in temperature levels, but light reduction has also been shown to have an important impact on  acquired  tolerance.  Since  the  lowest  temperatures  are commonly reached during the night hours in winter time and is an annually recurring event, a favorable trait for plants is the possibility of sensing an imminent cold period. Consequently, extensive crosstalk between light- and temperature signaling pathways has been demonstrated and in this review interesting interaction  points  that  have  been  previously  reported  in  the literature are highlighted.

  • 233.
    Lindlöf, Angelica
    et al.
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Bräutigam, Marcus
    Göteborg University.
    Chawade, Aakash
    Göteborg University.
    Olsson, Olof
    Göteborg University.
    Olsson, Björn
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre. Bioinformatik, Bioinformatics.
    Evaluation of combining several statistical methods with a flexible cutoff for identifying differentially expressed genes in pairwise comparison of EST sets2008In: Bioinformatics and Biology Insights, ISSN 1177-9322, E-ISSN 1177-9322, Vol. 2, p. 215-237Article in journal (Refereed)
    Abstract [en]

    The detection of differentially expressed genes from EST data is of importance for the discovery of potential biological or pharmaceutical targets, especially when studying biological processes in less characterized organisms and where large-scale microarrays are not an option. We present a comparison of five different statistical methods for identifying up-regulated genes through pairwise comparison of EST sets, where one of the sets is generated from a treatment and the other one serves as a control. In addition, we specifically address situations where the sets are relatively small (~2,000– 10,000 ESTs) and may differ in size. The methods were tested on both simulated and experimentally derived data, and compared to a collection of cold stress induced genes identified by microarrays. We found that combining the method pro- posed by Audic and Claverie with Fisher’s exact test and a method based on calculating the difference in relative frequency was the best combination for maximizing the detection of up-regulated genes. We also introduced the use of a flexible cutoff, which takes the size of the EST sets into consideration. This could be considered as an alternative to a static cutoff. Finally, the detected genes showed a low overlap with those identified by microarrays, which indicates, as in previous studies, low overall concordance between the two platforms.

  • 234.
    Lindlöf, Angelica
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Bräutigam, Marcus
    Department of Cell and Molecular Biology, Medicinaregatan 9C, Box 462, SE405 30 Göteborg, Sweden.
    Chawade, Aakash
    Department of Plant and Environmental Sciences, Gothenburg University, Box 461, SE405 30 Göteborg, Sweden.
    Olsson, Olof
    Department of Plant and Environmental Sciences, Gothenburg University, Box 461, SE405 30 Göteborg, Sweden.
    Olsson, Björn
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    In silico analysis of promoter regions from cold-induced genes in rice (Oryza sativa L.) and Arabidopsis thaliana reveals the importance of combinatorial control2009In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 25, no 11, p. 1345-1348Article in journal (Refereed)
    Abstract [en]

    Motivation:Cold acclimation involves a number of different cellularprocesses that together increase the freezing tolerance of anorganism. The DREB1/CBFs are transcription factors (TFs) thatare prominent in the regulation of cold responses in Arabidopsisthaliana, rice and many other crops. We investigated if theexpression of DREB1/CBFs and co-expressed genes relies on combinatorialcontrol by several TFs. Our results support this notion andindicate that methods for studying the regulation of complexcellular processes should include identification of combinationsof motifs, in addition to searching for individual overrepresentedbinding sites.

  • 235.
    Lindlöf, Angelica
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Chawade, Aakash
    CropTailor AB, Department of Pure and Applied Biochemistry, Lund University, Lund, Sweden / Department of Immunotechnology, Lund University, Lund, Sweden.
    Sikora, Per
    Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg, Sweden.
    Olsson, Olof
    CropTailor AB, Department of Pure and Applied Biochemistry, Lund University, Lund, Sweden / Department of Pure and Applied Biochemistry, Lund University, Lund, Sweden.
    Comparative Transcriptomics of Sijung and Jumli Marshi Rice during Early Chilling Stress Imply Multiple Protective Mechanisms2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0125385Article in journal (Refereed)
    Abstract [en]

    Introduction

    Low temperature is one of the major environmental factors that adversely affect plant growth and yield. Many cereal crops from tropical regions, such as rice, are chilling sensitive and, therefore, are affected already at <10°C. Interestingly, it has been demonstrated that chilling susceptibility varies greatly among rice varieties, which indicates differences in the underlying molecular responses. Understanding these differences is vital for continued development of rational breeding and transgenic strategies for more tolerant varieties. Thus, in this study, we conducted a comparative global gene expression profiling analysis of the chilling tolerant varieties Sijung and Jumli Marshi (spp. Japonica) during early chilling stress (<24 h, 10°C).

    Methods and Results

    Global gene expression experiments were conducted with Agilent Rice Gene Expression Microarray 4x44K. The analysed results showed that there was a relatively low (percentage or number) overlap in differentially expressed genes in the two varieties and that substantially more genes were up-regulated in Jumli Marshi than in Sijung but the number of down-regulated genes were higher in Sijung. In broad GO annotation terms, the activated response pathways in Sijung and Jumli Marshi were coherent, as a majority of the genes belonged to the catalytic, transcription regulator or transporter activity categories. However, a more detailed analysis revealed essential differences. For example, in Sijung, activation of calcium and phosphorylation signaling pathways, as well as of lipid transporters and exocytosis-related proteins take place very early in the stress response. Such responses can be coupled to processes aimed at strengthening the cell wall and plasma membrane against disruption. On the contrary, in Jumli Marshi, sugar production, detoxification, ROS scavenging, protection of chloroplast translation, and plausibly the activation of the jasmonic acid pathway were the very first response activities. These can instead be coupled to detoxification processes.

    Conclusions

    Based on the results inferred from this study, we conclude that different, but overlapping, strategies are undertaken by the two varieties to cope with the chilling stress; in Sijung the initial molecular responses seem to be mainly targeted at strengthening the cell wall and plasma membrane, whereas in Jumli Marshi the protection of chloroplast translation and detoxification is prioritized.

  • 236.
    Lindström, Tom
    et al.
    IFM Theory and Modelling, Linköping University, 581 83 Linköping, Sweden.
    Håkansson, Nina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Wennergren, Uno
    IFM Theory and Modelling, Linköping University, 581 83 Linköping, Sweden.
    The shape of the spatial kernel and its implications for biological invasions in patchy environments2011In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 278, no 1711, p. 1564-1571Article in journal (Refereed)
    Abstract [en]

    Ecological and epidemiological invasions occur in a spatial context. We investigated how these processes correlate to the distance dependence of spread or dispersal between spatial entities such as habitat patches or epidemiological units. Distance dependence is described by a spatial kernel, characterized by its shape (kurtosis) and width (variance). We also developed a novel method to analyse and generate point-pattern landscapes based on spectral representation. This involves two measures: continuity, which is related to autocorrelation and contrast, which refers to variation in patch density. We also analysed some empirical data where our results are expected to have implications, namely distributions of trees (Quercus and Ulmus) and farms in Sweden. Through a simulation study, we found that kernel shape was not important for predicting the invasion speed in randomly distributed patches. However, the shape may be essential when the distribution of patches deviates from randomness, particularly when the contrast is high. We conclude that the speed of invasions depends on the spatial context and the effect of the spatial kernel is intertwined with the spatial structure. This implies substantial demands on the empirical data, because it requires knowledge of shape and width of the spatial kernel, and spatial structure.

  • 237.
    Lindström, Tom
    et al.
    IFM, Theory and Modelling, Linköpings Universitet, Linköping, Sweden.
    Håkansson, Nina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Westerberg, Lars
    IFM, Biology, Linköpings Universitet, Linköping, Sweden.
    Wennergren, Uno
    IFM, Theory and Modelling, Linköpings Universitet, Linköping, Sweden.
    Splitting the tail of the displacement kernel shows the unimportance of kurtosis2008In: Ecology, ISSN 0012-9658, E-ISSN 1939-9170, Vol. 89, no 7, p. 1784-1790Article in journal (Refereed)
    Abstract [en]

    Animals disperse in space through different movement behaviors, resulting in different displacement distances. This is often described with a displacement kernel where the long-distance dispersers are within the tail of the kernel. A displacement with a large proportion of long-distance dispersers may have impact on different aspects of spatial ecology such as invasion speed, population persistence, and distribution. It is, however, unclear whether the kurtosis of the kernel plays a major role since a fatter tail also influences the variance of the kernel. We modeled displacement in landscapes with different amounts and configurations of habitats and handled kurtosis and variance separately to study how these affected population distribution and transition time. We conclude that kurtosis is not important for any of these aspects of spatial ecology. The variance of the kernel, on the other hand, was of great importance to both population distribution and transition time. We argue that separating variance and kurtosis can cast new light on the way in which long-distance dispersers are important in ecological processes. Consequences for empirical studies are discussed.

  • 238.
    Lindström, Tom
    et al.
    Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden / School of Biological Sciences, University of Sydney, Sydney, NSW, Australia.
    Sisson, Scott A.
    School of Mathematics and Statistics, University of New South Wales, Sydney, NSW, Australia.
    Håkansson, Nina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Bergman, Karl-Olof
    Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    Wennergren, Uno
    Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
    A spectral and Bayesian approach for analysis of fluctuations and synchrony in ecological datasets2012In: Methods in Ecology and Evolution, ISSN 2041-210X, E-ISSN 2041-210X, Vol. 3, no 6, p. 1019-1027Article in journal (Refereed)
    Abstract [en]

    Autocorrelation within ecological time series and synchrony between them may provide insight into the main drivers of observed dynamics. We here present methods that analyse autocorrelation and synchrony in ecological datasets using a spectral approach combined with Bayesian inference. To exemplify, we implement the method on dendrochronological data of the pedunculate oak (Quercus robur). The data consist of 110 years of growth of 10 live trees and seven trees that died during a synchronized oak death in Sweden in c. 2002-2007. We find that the highest posterior density is found for a noise colour of tree growth of gamma approximate to 0.95 (i.e. pink noise) with little difference between trees, suggesting climatic variation as a driving factor. This is further supported by the presence of synchrony, which we estimate based on phase-shift analysis. We conclude that the synchrony is time-scale dependent with higher synchrony at larger time-scales. We further show that there is no difference between the growth patterns of the alive and dead tree groups. This suggests that the trees were driven by the same factors prior to the synchronized death. We argue that this method is a promising approach for linking theoretical models with empirical data.

  • 239.
    Lindström, Tom
    et al.
    IFM Theory and Modelling, Linköping University.
    Sisson, Scott A.
    School of Mathematics and Statistics, University of New South Wales, Sydney.
    Nöremark, Maria
    Department of Disease Control and Epidemiology, SVA, National Veterinary Institute.
    Jonsson, Annie
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Wennergren, Uno
    IFM Theory and Modelling, Linköping University.
    Estimation of distance related probability of animal movements between holdings and implications for disease spread modeling2009In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 91, no 2-4, p. 85-94Article in journal (Refereed)
    Abstract [en]

    Between holding contacts are more common over short distances and this may have implications for the dynamics of disease spread through these contacts. A reliable estimation of how contacts depend on distance is therefore important when modeling livestock diseases. In this study, we have developed a method for analyzing distant dependent contacts and applied it to animal movement data from Sweden. The data were analyzed with two competing models. The first model assumes that contacts arise from a purely distance dependent process. The second is a mixture model and assumes that, in addition, some contacts arise independent of distance. Parameters were estimated with a Bayesian Markov Chain Monte Carlo (MCMC) approach and the model probabilities were compared. We also investigated possible between model differences in predicted contact structures, using a collection of network measures.

    We found that the mixture model was a much better model for the data analyzed. Also, the network measures showed that the models differed considerably in predictions of contact structures, which is expected to be important for disease spread dynamics. We conclude that a model with contacts being both dependent on, and independent of, distance was preferred for modeling the example animal movement contact data.

  • 240.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Enroth, Helena
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Claesson, Berndt E. B.
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ovemyr, Ida
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Karlsson, Jesper
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Fröberg, Berit
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Brodin, Anna-Karin
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Rune
    Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden..
    Karlsson, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, no 1, article id 199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis.

    METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity.

    RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results.

    CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

  • 241.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital / The swedish strategic program against antibiotic resistance.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis2017Conference paper (Refereed)
  • 242.
    Ljungström, Lars
    et al.
    Skaraborg Hospital Skövde, Sweden.
    Karlsson, Diana
    Skaraborg Hospital Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, R.
    Institute of Biosciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jacobsson, Gunnar
    Skaraborg Hospital Skövde, Sweden.
    Neutrophil to lymphocyte count ratio performs better than procalcitonin as a biomarker for bacteremia and severe sepsis in the emergency department2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no Suppl 1, article id P66Article in journal (Refereed)
  • 243.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden / CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden.
    Andersson, Rune
    CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden / Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Usener, Barbara
    Department of Clinical Chemistry, Unilabs AB, Skövde, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e018704Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.

    METHODS:

    Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).

    RESULTS:

    For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).

    CONCLUSIONS:

    Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

  • 244.
    Ljungström, Lars R.
    et al.
    Department of Infectious Diseases, Skaraborg Hospital / CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde / CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg.
    Claesson, Berndt E. B.
    Department of Clinical Microbiology, Unilabs, Skaraborg Hospital, Skövde.
    Andersson, Rune
    CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Molecular Microbiology, Unilabs, Skaraborg Hospital, Skövde.
    Respiratory viral infections are underdiagnosed in patients with suspected sepsis2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, p. 1767-1776Article in journal (Refereed)
    Abstract [en]

    The study aim was to investigate the prevalence and clinical relevance of viral findings by multiplex PCR from the nasopharynx of clinically septic patients during a winter season. During 11 weeks of the influenza epidemic period in January-March 2012, consecutive adult patients suspected to be septic (n = 432) were analyzed with cultures from blood and nasopharynx plus multiplex PCR for respiratory viruses on the nasopharyngeal specimen. The results were compared with those from microbiology analyses ordered as part of standard care. During the winter season, viral respiratory pathogens, mainly influenza A virus, human metapneumovirus, coronavirus, and respiratory syncytial virus were clinically underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the first four weeks of the influenza epidemic, few tests for influenza were ordered by clinicians, indicating low awareness that the epidemic had started. Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by culture correlated to pneumonia diagnosis, and in those patients laboratory signs of viral co-infections were common but rarely suspected by clinicians. The role of respiratory viral infections in patients presenting with a clinical picture of sepsis is underestimated. Specific antiviral treatment might be beneficial in some cases and may reduce spread in a hospital setting. Diagnosing viral infections may promote reduction of unnecessary antibiotic use. It can also be a tool for decisions concerning patient logistics, in order to minimize exposure of susceptible patients and personnel.

  • 245.
    Lloyd, Donna M.
    et al.
    Institute of Psychological Sciences, University of Leeds, Leeds, UK.
    Gillis, Victoria
    School of Psychological Sciences, University of Manchester, Manchester, UK.
    Lewis, Elizabeth
    School of Psychological Sciences, University of Manchester, Manchester, UK.
    Farrell, Martin J.
    School of Psychological Sciences, University of Manchester, Manchester, UK.
    Morrison, India
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre. Department of Clinical Neurophysiology, Sahlgrenska University Hospital, Gothenburg, Sweden / Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
    Pleasant touch moderates the subjective but not objective aspects of body perception2013In: Frontiers in Behavioral Neuroscience, ISSN 1662-5153, E-ISSN 1662-5153, Vol. 7, no Dec, article id 207Article in journal (Refereed)
    Abstract [en]

    Un-myelinated C tactile afferents (CT afferents) are a key finding in affective touch. These fibers, which activate in response to a caress-like touch to hairy skin (CT afferents are not found in palm skin), may have more in common with interoceptive systems encoding body ownership, than afferent systems processing other tactile stimuli. We tested whether subjective embodiment of a rubber hand (measured through questionnaire items) was increased when tactile stimulation was applied to the back of the hand at a rate optimal for CT afferents (3 cm/s) vs. stimulation of glabrous skin (on the palm of the hand) or at a non-optimal rate (30 cm/s), which should not activate these fibers. We also collected ratings of tactile pleasantness and a measure of perceived limb position, proprioceptive drift, which is mediated by different mechanisms of multisensory integration than those responsible for feelings of ownership. The results of a multiple regression analysis revealed that proprioceptive drift was a significant predictor of subjective strength of the illusion when tactile stimuli were applied to the back of the hand, regardless of stroking speed. This relationship was modified by pleasantness, with higher ratings when stimulation was applied to the back of the hand at the slower vs. faster stroking speed. Pleasantness was also a unique predictor of illusion strength when fast stroking was applied to the palm of the hand. However, there were no conditions under which pleasantness was a significant predictor of drift. Since the illusion was demonstrated at a non-optimal stroking speed an integrative role for CT afferents within the illusion cannot be fully supported. Pleasant touch, however, does moderate the subjective aspects of the rubber hand illusion, which under certain tactile conditions may interact with proprioceptive information about the body or have a unique influence on subjective body perception.

  • 246.
    Lubovac, Zelmina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Investigating Topological and Functional Features of Multimodular Proteins2009In: Journal of Biomedicine and Biotechnology, ISSN 1110-7243, E-ISSN 1110-7251, p. Article Number: 472415-Article in journal (Refereed)
    Abstract [en]

    To generate functional modules as functionally and structurally cohesive formations in protein interaction networks (PINs) constitutes an important step towards understanding how modules communicate on a higher level of the PIN organisation that underlies cell functionality. However, we need to understand how individual modules communicate and are organized into the higher-order structure(s) of the PIN organization that underlies cell functionality. In an attempt to contribute to this understanding, we make an assumption that the proteins reappearing in several modules, termed here as multimodular proteins (MMPs), may be useful in building higher-order structure(s) as they may constitute communication points between different modules. In this paper, we investigate common properties shared by these proteins and compare them with the properties of so called single-modular proteins (SMPs) by analyzing three aspects: functional aspect, that is, annotation of the proteins, topological aspect that is betweenness centrality of the proteins, and lethality. Furthermore, we investigate the interconnectivity role of some proteins that are identified as functionally and topologically important.

  • 247.
    Lubovac, Zelmina
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Gamalielsson, Jonas
    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.
    Combining functional and topological properties to identify core modules in protein interaction networks2006In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 64, no 4, p. 948-959Article in journal (Refereed)
    Abstract [en]

    Advances in large-scale technologies in proteomics, such as yeast two-hybrid screening and mass spectrometry, have made it possible to generate large Protein Interaction Networks (PINs). Recent methods for identifying dense sub-graphs in such networks have been based solely on graph theoretic properties. Therefore, there is a need for an approach that will allow us to combine domain-specific knowledge with topological properties to generate functionally relevant sub-graphs from large networks. This article describes two alternative network measures for analysis of PINs, which combine functional information with topological properties of the networks. These measures, called weighted clustering coefficient and weighted average nearest-neighbors degree, use weights representing the strengths of interactions between the proteins, calculated according to their semantic similarity, which is based on the Gene Ontology terms of the proteins. We perform a global analysis of the yeast PIN by systematically comparing the weighted measures with their topological counterparts. To show the usefulness of the weighted measures, we develop an algorithm for identification of functional modules, called SWEMODE (Semantic WEights for MODule Elucidation), that identifies dense sub-graphs containing functionally similar proteins. The proposed method is based on the ranking of nodes, i.e., proteins, according to their weighted neighborhood cohesiveness. The highest ranked nodes are considered as seeds for candidate modules. The algorithm then iterates through the neighborhood of each seed protein, to identify densely connected proteins with high functional similarity, according to the chosen parameters. Using a yeast two-hybrid data set of experimentally determined protein-protein interactions, we demonstrate that SWEMODE is able to identify dense clusters containing proteins that are functionally similar. Many of the identified modules correspond to known complexes or subunits of these complexes.

  • 248.
    Lubovac-Pilav, Zelmina
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Integrative Approach for Detection of Functional Modules from Protein-Protein Interaction Networks2012In: Protein-Protein Interactions: Computational and Experimental Tools / [ed] Weibo Cai & Hao Hong, INTECH, 2012, p. 97-112Chapter in book (Refereed)
  • 249.
    Lubovac-Pilav, Zelmina
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Borràs, Daniel M.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ponce, Esmeralda
    Dominican University of California, United States of America.
    Louie, Maggie C.
    Dominican University of California, United States of America / College of Pharmacy, Touro University of California, United States of America .
    Using expression profiling to understand the effects of chronic cadmium exposure on mcf-7 breast cancer cells2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84646Article in journal (Refereed)
    Abstract [en]

    Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.

  • 250.
    Lundh, Dan
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Coleman, Scott
    Baylor University Medical Center, Dallas, USA.
    Riad, Jacques
    Orthopedic Department, Skaraborgs Hospital, Skövde, Sweden.
    Addressing homogeneity between affected and unaffected sides and upper and lower extremities in unilateral cerebral palsy2012In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 36, no Supplement 1, p. S14-S15Article in journal (Refereed)
2345678 201 - 250 of 474
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf