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  • 1.
    Wallner, Fredrik K.
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Redoxis AB, Lund, Sweden.
    Hultqvist Hopkins, Malin
    Redoxis AB, Lund, Sweden.
    Lindvall, Therese
    Redoxis AB, Lund, Sweden.
    Olofsson, Peter
    Redoxis AB, Lund, Sweden.
    Tilevik, Andreas
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Cytokine correlation analysis based on drug perturbation2017Ingår i: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 90, 73-79 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytokines and chemokines play a crucial role in regulating the immune system. Understanding how these molecules are co-regulated is important to understand general immunology, and particularly their role in clinical applications such as development and evaluation of novel drug therapies. Cytokines are today widely used as therapeutic targets and as biomarkers to monitor effects of drug therapies and for prognosis and diagnosis of diseases. Therapies that target a specific cytokine are also likely to affect the production of other cytokines due to their cross-regulatory functions and because the cytokines are produced by common cell types. In this study, we have perturbated the production of 17 different cytokines in a preclinical rat model of autoimmune arthritis, using 55 commercially available immunomodulatory drugs and clinical candidates. The majority of the studied drugs was selected for their anti-inflammatory role and was confirmed to inhibit the production of IL-2 and IFN-γ in this model but was also found to increase the production of other cytokines compared to the untreated control. Correlation analysis identified 58 significant pairwise correlations between the cytokines. The strongest correlations found in this study were between IL-2 and IFN-γ (r=0.87) and between IL-18 and EPO (r=0.84). Cluster analysis identified two robust clusters: (1) IL-7, IL-18 and EPO, and (2) IL-2, IL-17 and IFN-γ. The results show that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy.

  • 2.
    Kajonius, Petri J.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Gothenburg, Sweden / Department of Behavioral Sciences, University West, Sweden.
    Cross-cultural personality differences between East Asia and Northern Europe in IPIP-NEO2017Ingår i: International Journal of Personality Psychology, E-ISSN 2451-9243, Vol. 3, nr 1, 1-7 s.Artikel i tidskrift (Refereegranskat)
  • 3.
    Starokozhko, Viktoriia
    et al.
    Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
    Vatakuti, Suresh
    Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
    Schievink, Bauke H.
    Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
    Merema, Marjolijn T.
    Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
    Asplund, Annika
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Aspegren, Anders
    Takara Bio Europe AB, Gothenburg, Sweden.
    Groothuis, Geny M. M.
    Division of Pharmacokinetics Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, Groningen, The Netherlands.
    Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days2017Ingår i: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 91, nr 5, 2079-2092 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 days of incubation. hPCLS were incubated in two media developed for long-term culture of hepatocytes, RegeneMed(®), and Cellartis(®), and in the standard medium WME. Maintenance of phase I and II metabolism was studied both on gene expression as well as functional level using a mixture of CYP isoform-specific substrates. Albumin synthesis, morphological integrity, and glycogen storage was assessed, and gene expression was studied by transcriptomic analysis using microarrays with a focus on genes involved in drug metabolism, transport and toxicity. The data show that hPCLS retain their viability and functionality during 5 days of incubation in Cellartis(®) medium. Albumin synthesis as well as the activity and gene expression of phase I and II metabolic enzymes did not decline during 120-h incubation in Cellartis(®) medium, with CYP2C9 activity as the only exception. Glycogen storage and morphological integrity were maintained. Moreover, gene expression changes in hPCLS during incubation were limited and mostly related to cytoskeleton remodeling, fibrosis, and moderate oxidative stress. The expression of genes involved in drug transport, which is an important factor in determining the intracellular xenobiotic exposure, was also unchanged. Therefore, we conclude that hPCLS cultured in Cellartis(®) medium are a valuable human ex vivo model for toxicological and pharmacological studies that require prolonged xenobiotic exposure.

  • 4.
    Kajonius, Petri J.
    et al.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Gothenburg, Sweden / Department of Social and Behavioral Studies, University West, Sweden.
    Carlander, Anders
    Department of Psychology, University of Gothenburg, Sweden / Centre for Finance, School of Business, Economics and Law, University of Gothenburg, Sweden.
    Who gets ahead in life?: Personality traits and childhood background in economic success2017Ingår i: Journal of Economic Psychology, ISSN 0167-4870, E-ISSN 1872-7719, Vol. 59, 164-170 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In many societies around the world, the ideal is that anyone can achieve a successful lifeindependent of family background. An indication of such social mobility could be that personalitycharacteristics have stronger impact than childhood background on economic success.The present study investigated how much of life outcomes (i.e., educationalattainment, annual income, and life outcome satisfaction) were accounted for by adult personalitytraits (the Big Five), when controlled for childhood socio-economic status (SES).The results from a large, representative Swedish sample (N = 5280) showed that personalitytraits (especially neuroticism) were associated as much as or more than childhood SESto annual income and life outcome satisfaction, whereas childhood SES related more toeducational attainment. These results may help facilitate our understanding of the mechanismsbehind individual economic success.

  • 5.
    Howell, Daniel
    et al.
    Institute of Marine Research, Nordnes, Norway.
    Kempf, Alexander
    Thuenen Institute of Sea Fisheries, Hamburg, Germany.
    Bauer, Barbara
    Baltic Sea Centre, Stockholm, Sweden.
    Belgrano, Andrea
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Institute of Marine Research, Lysekil, Sweden.
    Thorpe, Robert
    Centre for Environment, Fisheries and Aquaculture Science (CEFAS), Suffolk, United Kingdom.
    Vinther, Morten
    DTU-Aqua, Charlottenlund, Denmark.
    Bartolino, Valerio
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Lysekil, Sweden.
    Pope, John
    NRC (Europe) Ltd.
    Lehuta, Sigrid
    French Institute of Research for the Exploitation of the sea (Ifremer), Nantes, France.
    Gaichas, Sarah
    NOAA Northeast Fisheries Science Center, Woods Hole, USA.
    Lucey, Sean
    Dept. of Commerce/NOAA/NMFS Northeast Fisheries Science Center, Woods Hole, USA.
    Norrström, Niclas
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Spence, Michael
    Department of Animal and Plant Sciences, Sheffield, United Kingdom.
    Holmgren, Noél
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Villanueva, Ching
    French Institute of Research for the Exploitation of the Sea (Ifremer), Nantes, France.
    Poos, Jan Jaap
    Wageningen Marine Research, Ijmuiden, the Netherlands.
    Kulatska, Nataliia
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Institute of Marine Research, Lysekil, Sweden.
    Report of the Working Group on Multispecies Assessment Methods (WGSAM), 10-14 October 2016, Reykjavik, Iceland2017Rapport (Övrigt vetenskapligt)
    Abstract [en]

    The Working Group on Multispecies Assessment Methods (WGSAM) met in Reykjavik, Iceland, 10–14 October 2016. In this tenth report of the pan-regional WGSAM, work focused on four (B, E, F, G) of the multi-annual ToRs.

    Based on their knowledge, participants provided an updated inventory of progress of multispecies models in ICES Ecoregions (ToR A), noting those regions where no information was available. Reporting on ToR A was scarce compared to previous years, partly because recent relevant work was reported against ToR E and G instead.

    A Key Run (ToR B) of the Baltic Sea Ecopath with Ecosim (NS-EwE) model was presented and reviewed in detail by 4 WGSAM experts, and approved by the group following implementation of changes agreed in plenary at the meeting and verified by the 4 experts in January. The Key Run is documented in a detail in Annex 3, with key outputs summarised in Section 3 and data files made available on the WGSAM webpage). WGSAM also conducted an informal review of the LeMans modelling framework for potential application in the Irish Sea, and recommended adjustments to the framework for further review. Because the LeMans framework is a within-model ensemble addressing parameter uncertainty, this review also related to ToR D.

    Multispecies model skill assessment (ToR C) and multi-model ensemble methods (ToR D) were not emphasized this year. However, plans were made to coordinate future work for ToR C, and one ToR D presentation reviewed the utility of a dynamic multimodel ensemble for making inferences about the real world. This method can infer results for individual components of aggregate groups; the ensemble model uses correlations in other ecosystem models to determine what the models that group species would have predicted for individual species. A proof of concept for the North Sea was presented.

    Ecosystem indicator analyses (ToR E) were presented from a wide range of ecosystems. A theoretical analysis comparing results from the Celtic and North Seas with 4 “idealized” fleets was presented to analyse the performance of selected indicators in a multispecies mixed fishery. Four indicators including the Large Fish Indicator (LFI) were examined, and shown to have mixed utility in measuring the impact of different fleet sectors, with the best indicator varying by ecosystem. A multivariate analysis of ecosystem responses to multiple drivers was conducted for four US ecosystems using gradient forest method to identify potential ecosystem thresholds. Other multivariate methods were reviewed that draw on the strengths of multiple indicators for the Northeast US shelf ecosystem. A food web based biodiversity indicator was presented with an application for the Baltic Sea. This could be extended to any ecosystem with an EwE or similar model. A community status indicator relating a species-area relationship to the LFI and mean trophic levels was presented for the Swedish west coast.

    Impacts of apex predators on fisheries (ToR F) were examined with one presentation and a group discussion planning further work. A multipecies production model was parameterized to simulate interactions between three fish guilds, fisheries, and one marine mammal guild, concluding that fish reference points and trajectories change with marine mammal interactions. Fishery management was also important to reduce vessel interactions with and ensure prey supply to marine mammals. 4 | ICES WGSAM REPORT 2016 Exploration of practical advice for fisheries management incorporating multispecies, mixed fishery, and environmental factors (ToR G) was evident across regions. Two approaches for incorporating species, fleet, environmental, and other interactions are in progress in the Northeast US. One presentation outlined the New England approach, and another outlined the Mid-Atlantic approach. In New England, a management strategy evaluation is in progress to evaluate harvest control rules that consider herring's role as forage in the ecosystem. The modelling framework and stakeholder workshops were discussed. In the Baltic, a Nash Equilibrium optimisation approach incorporating environmental factors was presented for the cod-herring-sprat fishery to attempt to identify a solution that would give good yield for all species simultaneously. In the North Sea a theoretical analysis using 4 “idealized” fleets was presented to analyse the potential implications of "Pretty Good Yield" ranges around MSY. The model examined the likelihood of the fishery being precautionary for the different species given the uncertainties involved, and concluded that the upper ends of MSY ranges would not guarantee precautionarity.

  • 6.
    McBean, G. J.
    et al.
    School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.
    López, M. G.
    Instituto Teófilo Hernando for Drug Discovery, Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
    Wallner, Fredrik K.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Redoxis AB.
    Redox-based therapeutics in neurodegenerative disease2017Ingår i: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 174, nr 12, 1750-1770 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This review describes recent developments in the search for effective therapeutic agents that target redox homeostasis in neurodegenerative disease. The disruption to thiol redox homeostasis in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis is discussed, together with the experimental strategies that are aimed at preventing, or at least minimizing, oxidative damage in these diseases. Particular attention is given to the potential of increasing antioxidant capacity by targeting the Nrf2 pathway, the development of inhibitors of NADPH oxidases that are likely candidates for clinical use, together with strategies to reduce nitrosative stress and mitochondrial dysfunction. We describe the shortcomings of compounds that hinder their progression to the clinic and evaluate likely avenues for future research.

  • 7.
    Retz, Karolina
    et al.
    Department of Clinical Microbiology, Unilabs AB, Skövde.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Andersson, Carl
    Högskolan i Skövde.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Ljungström, Lars
    The Skaraborg Hospital, Skövde, Sweden .
    Enroth, Helena
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde .
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting2017Konferensbidrag (Refereegranskat)
  • 8.
    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
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis2017Konferensbidrag (Refereegranskat)
  • 9.
    Norrström, Niclas
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Casini, Michele
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Institute of Marine Research, Lysekil, Sweden.
    Holmgren, Noél M. A.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Nash equilibrium can resolve conflicting maximum sustainable yields in multi-species fisheries management2017Ingår i: ICES Journal of Marine Science, ISSN 1054-3139, E-ISSN 1095-9289, Vol. 74, nr 1, 78-90 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The current fisheries management goals set by the European Commission states that fish stocks should be harvested to deliver maximum sustainable yields (MSY) and simultaneously, management should take ecosystem considerations into account. This creates unsolved trade-offs for the management of the stocks. We suggest a definition of a multi-species-MSY (MS-MSY) where no alternative fishing mortality (F) can increase yield (long term) for any ecologically interacting stock, given that the other stocks are fished at constant efforts (Fs). Such a MS-MSY can be solved through the game theoretic concept of a Nash equilibrium and here we explore two solutions to this conflict in the Baltic Sea. We maximize the sustainable yield of each stock under two constraints: first, we harvest the other stocks at a fixed F (FNE); second, we keep the spawning stock biomasses of the other stocks fixed [biomass Nash equilibrium (BNE)]. As a case study, we have developed a multi-species interaction stochastic operative model (MSI-SOM), which contains a SOM for each of the three dominant species of the Baltic Sea, the predator cod (Gadus morhua), and its prey herring (Clupea harengus), and sprat (Sprattus sprattus). For our Baltic Sea case, MS-MSYs exist under both the FNE and the BNE, but there is no guarantee that point solutions exists. We found that the prey species’ spawning stock biomasses are additive in the cod growth function, which allowed for a point solution in BNE. In the FNE, the herring MSY was found to be relatively insensitive to the other species’ fishing mortalities (F), which facilitated a point solution. The MSY targets of the BNE and the FNE differ slightly where the BNE gives higher predator yields and lower prey yields.

  • 10.
    Kazemi, Ali
    et al.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    Kajonius, Petri
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Variations in user-oriented elderly care: a multilevel approach2017Ingår i: International Journal of Quality and Service Sciences, ISSN 1756-669X, E-ISSN 1756-6703, Vol. 9, nr 2, 138-147 s.Artikel i tidskrift (Refereegranskat)
  • 11.
    Orio, Alessandro
    et al.
    SLU, Sweden.
    Nielsen, Anders
    DTU Aqua, Denmark.
    Luzenczyk, Anna
    Morski Instytut Rybacki, Poland.
    Berg, Casper
    DTU Aqua, Denmark.
    Ustups, Didzis
    BIOR, Latvia.
    Artemenkov, Dmitriy
    Russian Federal Research Institute of Fisheries and Oceanography, Russia.
    Schade, Franziska
    Thünen-Institut, Germany.
    Kornilovs, Georgs
    BIOR, Latvia.
    Degel, Henrik
    DTU Aqua, Denmark.
    Strehlow, Harry
    Thünen-Institut, Germany.
    Karpushevskiy, Igor
    AtlantNIRO, Russia.
    Horbowy, Jan
    Morski Instytut Rybacki, Poland.
    Raitaniemi, Jari
    Luke Natural Resources Institute, Finland.
    Boje, Jesper
    DTU Aqua, Denmark.
    Hjelm, Joakim
    SLU, Sweden.
    Lövgren, Johan
    SLU, Sweden.
    Pönni, Jukka
    Luke Natural Resources Institute, Finland.
    Hommik, Kristiina
    Öhman, Kristin
    SLU, Sweden.
    Eero, Margit
    DTU Aqua, Denmark.
    Storr-Paulsen, Marie
    DTU Aqua, Denmark.
    Plikshs, Maris
    BIOR, Latvia.
    Casini, Michele
    SLU, Sweden.
    Bergenius, Mikaela
    SLU, Sweden.
    Mosegaard, Henrik
    Holmgren, Noel
    SLU, Sweden.
    Norrström, Niclas
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Kaljuste, Olavi
    SLU, Sweden.
    Jounela, Pekka
    Luke Natural Resources Institute, Finland.
    Statkus, Romas
    Lithuania.
    Jonusas, Stanislovas
    European Commission.
    Neuenfeldt, Stefan
    DTU Aqua, Denmark.
    Stoetera, Sven
    Thünen-Institut, Germany.
    Raid, Tiit
    University of Tartu, Estonia.
    Mildenberger, Tobias
    DTU Aqua, Denmark.
    Gröhsler, Tomas
    Thünen-Institut, Germany.
    Krumme, Uwe
    Thünen-Institut, Germany.
    Amosova, Viktoriia
    AtlantNIRO, Russia.
    Grygiel, Wlodzimierz
    Morski Instytut Rybacki, Poland.
    Pekcan-Hekim, Zeynep
    SLU, Sweden.
    Mirny, Zuzanna
    Morski Instytut Rybacki, Poland.
    Report of the Baltic Fisheries AssessmentWorking Group (WGBFAS): 19-26 April 2017, Copenhagen, Denmark2017Rapport (Övrigt vetenskapligt)
    Abstract [en]

    The ICES Baltic Fisheries Assessment Working Group (WGBFAS) met 19-26 April 2017(Chair: Tomas Gröhsler, Germany and Co-chair: Michele Casini, Sweden), with 41 participants and 9 countries represented. The objective of WGBFAS was to assess the status of the following stocks: Sole in Division 3.a, SDs 20–24; Cod in Kattegat, Cod in SDs 22–24, Cod in SDs 25–32; Herring in SDs 25–27, 28.2, 29 and 32, Herring in SD 28.1 (Gulf of Riga), Herring in SDs 30-31 (Gulf of Bothnia); Sprat in SDs 22–32; Plaice in SDs 21–23, Plaice in SDs 24–25; Flounder in SDs 22–23, in SDs 24–25, in SDs 26+28 and SDs 27+29–32; Brill in SDs 22–32, Dab in SDs 22–32 and Turbot in SDs 22–32. WGBFAS also identified the data needed for next year’s data call with some suggestions for improvements in the data call, and stock-specific research needs.The report contains an introduction with the summary of other WGs relevant for the WGBFAS, the methods used, and ecosystem considerations. The results of the analytical stock assessment or survey trends for the species listed above are then presented with all the stocks with the same species in the same sections. The report ends with references, recommendations, links to Stock Annexes and list of Working Documents.The principle analytical models used for the stock assessments were XSA and SAM. For most flatfishes and cod in SDs 25–32 (data limited stocks), CPUE trends from bottomtrawl surveys were used in the assessment (except plaice in SDs 24–25 for which relative SSB from SAM was used). For the data limited stocks, reference points based on length-based indicators were estimated (except cod in SDs 25-32 for which relative reference points were estimated using the SPiCT model). For cod in SDs 25–32, intersessional work was planned to hopefully allow returning to an analytical stock assessment in the near future. Ecosystem changes have been analytically considered in the following stock assessments: Herring in SD 25–27, 28.2, 29 and 32, and Sprat in SD 22–32, in form of cod predation mortality.

  • 12.
    Olsson, Björn E.
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Korsakova, Ekaterina S.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Anan'ina, Lyudmila N.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Pyankova, Anna A.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Olga V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Plotnikova, Elena G.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Dmitri V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Draft genome sequences of strains Salinicola socius SMB35T, Salinicola sp. MH3R3–1 and Chromohalobacter sp. SMB17 from the Verkhnekamsk potash mining region of Russia2017Ingår i: Standards in Genomic Sciences, ISSN 1944-3277, E-ISSN 1944-3277, Vol. 12, nr 39, 1-13 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Halomonads are moderately halophilic bacteria that are studied as models of prokaryotic osmoadaptation and sources of enzymes and chemicals for biotechnological applications. Despite the progress in understanding the diversity of these organisms, our ability to explain ecological, metabolic, and biochemical traits of halomonads at the genomic sequence level remains limited. This study addresses this gap by presenting draft genomes of Salinicola socius SMB35T, Salinicola sp. MH3R3-1 and Chromohalobacter sp. SMB17, which were isolated from potash mine tailings in the Verkhnekamsk salt deposit area of Russia. The analysis of these genomes confirmed the importance of ectoines and quaternary amines to the capacity of halomonads to tolerate osmotic stress and adapt to hypersaline environments. The study also revealed that Chromohalobacter and Salinicola share 75-90% of the predicted proteome, but also harbor a set of genus-specific genes, which in Salinicola amounted to approximately 0.5 Mbp. These genus-specific genome segments may contribute to the phenotypic diversity of the Halomonadaceae and the ability of these organisms to adapt to changing environmental conditions and colonize new ecological niches.

  • 13.
    Sikka, Pilleriin
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Feilhauer, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    How You Measure Is What You Get: Differences in Self- and External Ratings of Emotional Experiences in Home Dreams2017Ingår i: American Journal of Psychology, ISSN 0002-9556, E-ISSN 1939-8298, Vol. 130, nr 3, 367-384 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study demonstrates that different methods for measuring emotional experiences in dreams — self-ratings of dreams using emotion rating scales versus external ratings in the form of content analysis of narrative dream reports — can lead to strikingly different results and contradicting conclusions about the emotional content of home dreams. During 3 consecutive weeks, every morning upon awakening, 44 participants (16 men, 28 women, average age 26.9± 5.1 years) reported their dreams and rated their emotional experiences in those dreams using the modified Differential Emotions Scale. Two external judges rated emotional experiences inthe same 552 (M = 12.55 ± 5.72) home dream reports using the same scale. Comparison of the 2 methods showed that with self-ratings dreams were rated as more emotional and more positive than with external ratings. Moreover, whereas with self-ratings the majority of dreams was rated as positively valenced, with external ratings the majority of dream reports was rated as negatively valenced. Although self- and external ratings converge, at least partially, in the measurement of negative emotional experiences, they diverge greatly in the measurement of positive emotional experiences. On one hand, this discrepancy may result from different biases inherent in the 2 measurement methods highlighting the need to develop better methods for measuring emotional experiences. On the other hand, self- and external ratings may capture different phenomena and should thus be considered complementary and used concurrently. Nevertheless, results suggest that negative emotional experiences can be measured in a more valid and reliable manner than positive emotional experiences.

  • 14.
    Helldin, Tove
    et al.
    Högskolan i Skövde, Institutionen för informationsteknologi. Högskolan i Skövde, Forskningscentrum för Informationsteknologi. University of Skövde.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Towards a Clinical Support System for the Early Diagnosis of Sepsis2017Ingår i: International Conference on Digital Human Modeling and Applications in Health, Safety, Ergonomics and Risk Management: DHM 2017: Digital Human Modeling. Applications in Health, Safety, Ergonomics, and Risk Management: Health and Safety, Cham: Springer, 2017, 23-35 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Early and accurate diagnosis of sepsis is critical for patientsafety. However, this is a challenging task due to the very general symptomsassociated with sepsis, the immaturity of the tools used by theclinicians as well as the time-delays associated with the diagnostic methodsused today. This paper explores current literature regarding guidelinesfor clinical decision support, and support for sepsis diagnosis inparticular, together with guidelines extracted from interviews with fourclinicians and one biomedical analyst working at a hospital and clinicallaboratory in Sweden. The results indicate the need for the developmentof visual and interactive aids for enabling early and accurate diagnosisof sepsis.

  • 15.
    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
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. University of Turku, Turku, Finland.
    Different Electrophysiological Correlates of Visual Awareness for Detection and Identification2017Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, nr 9, 1621-1631 s.Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Skillbäck, Tobias
    et al.
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Delsing, Louise
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap. Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Mattsson, Niklas
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden / Department of Neurology, Skåne University Hospital, Lund, Sweden.
    Janelidze, Shorena
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Nägga, Katarina
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Kilander, Lena
    Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Wimo, Anders
    Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden.
    Winblad, Bengt
    Division for Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden / Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden.
    Hansson, Oskar
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden / Department of Neurology, Skåne University Hospital, Lund, Sweden.
    Blennow, Kaj
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Eriksdotter, Maria
    Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden / Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
    Zetterberg, Henrik
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden / Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK / UK Dementia Research Institute at UCL, London, UK.
    CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 59, 1-9 s., S0197-4580(17)30230-0Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology.

  • 17.
    Wobst, Heike J
    et al.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Wesolowski, Steven S
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Chadchankar, Jayashree
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Delsing, Louise
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. IMED Biotech Unit, AstraZeneca Discovery Science, Mölndal, Sweden.
    Jacobsen, Steven
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Mukherjee, Jayanta
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Deeb, Tarek Z
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Dunlop, John
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Brandon, Nicholas J
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Moss, Stephen J
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States / Department of Neuroscience, Tufts University School of Medicine, Boston, United States.
    Cytoplasmic Relocalization of TAR DNA-Binding Protein 43 Is Not Sufficient to Reproduce Cellular Pathologies Associated with ALS In vitro.2017Ingår i: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, 46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in the gene TARDBP, which encodes TAR DNA-binding protein 43 (TDP-43), are a rare cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While the majority of mutations are found in the C-terminal glycine-rich domain, an alanine to valine amino acid change at position 90 (A90V) in the bipartite nuclear localization signal (NLS) of TDP-43 has been described. This sequence variant has previously been shown to cause cytoplasmic mislocalization of TDP-43 and decrease protein solubility, leading to the formation of insoluble aggregates. Since the A90V mutation has been described both in patients as well as healthy controls, its pathogenic potential in ALS and FTD remains unclear. Here we compare properties of overexpressed A90V to the highly pathogenic M337V mutation. Though both mutations drive mislocalization of the protein to the cytoplasm to the same extent, M337V produces more significant damage in terms of protein solubility, levels of pathogenic phosphorylation, and formation of C-terminal truncated protein species. Furthermore, the M337V, but not the A90V mutant, leads to a downregulation of histone deacetylase 6 and Ras GTPase-activating protein-binding protein. We conclude that in the absence of another genetic or environmental 'hit' the A90V variant is not sufficient to cause the deleterious phenotypes associated with ALS and FTD, despite prominent cytoplasmic protein relocalization of TDP-43.

  • 18.
    Wobst, Heike J
    et al.
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States.
    Delsing, Louise
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. AstraZeneca, Discovery Science, Innovative Medicines and Early Development Biotech Unit, Mölndal, Sweden.
    Brandon, Nicholas J
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States / AstraZeneca, Neuroscience, Innovative Medicines and Early Development, Waltham, United States.
    Moss, Stephen J
    AstraZeneca, Tufts Laboratory for Basic and Translational Neuroscience, Tufts University, Boston, United States / Department of Neuroscience, Tufts University, School of Medicine, Boston, MA, United States.
    Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant.2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 5, e0177181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The RNA-binding and -processing protein TAR DNA-binding protein 43 (TDP-43) is heavily linked to the underlying causes and pathology of neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In these diseases, TDP-43 is mislocalized, hyperphosphorylated, ubiquitinated, aggregated and cleaved. The importance of TDP-43 cleavage in the disease pathogenesis is still poorly understood. Here we detail the use of D-sorbitol as an exogenous stressor that causes TDP-43 cleavage in HeLa cells, resulting in a 35 kDa truncated product that accumulates in the cytoplasm within one hour of treatment. We confirm that the formation of this 35 kDa cleavage product is mediated by the activation of caspases. Inhibition of caspases blocks the cleavage of TDP-43, but does not prevent the accumulation of full-length protein in the cytoplasm. Using D-sorbitol as a stressor and caspase activator, we also demonstrate that the A90V variant of TDP-43, which lies adjacent to the caspase cleavage site within the nuclear localization sequence of TDP-43, confers partial resistance against caspase-mediated generation of the 35 kDa cleavage product.

  • 19.
    Bays, Harold E.
    et al.
    Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY, USA.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Global Medicines Development, CVMD, AstraZeneca, Gothenburg, Sweden.
    Xu, John
    Biometrics and Information Sciences, AstraZeneca, Gaithersburg, MD, USA.
    Sjöstrom, Carl David
    Global Medicines Development, CVMD, AstraZeneca, Gothenburg, Sweden.
    Underberg, James A.
    Department of Medicine, NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease, New York, NY, USA.
    Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels2017Ingår i: Journal of Clinical Lipidology, ISSN 1933-2874, E-ISSN 1876-4789, Vol. 11, nr 2, 450-458 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption.

    OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels.

    METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (>= 150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria.

    RESULTS: The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups.

    CONCLUSION: Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors. 

  • 20.
    Sikka, Pilleriin
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Sandman, Nils
    Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland / The Genomics and Biomarkers Unit, National Institute for Health and Welfare, Finland.
    Tuominen, Jarno
    Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Dream emotions: a comparison of home dream reports with laboratory early and late REM dream reports2017Ingår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, 1-9 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to compare the emotional content of dream reports collected at home upon morning awakenings with those collectedin the laboratory upon early and late rapid eye movement (REM) sleep awakenings. Eighteen adults (11 women, seven men; mean age = 25.89 ± 4.85) wrote down their home dreams every morning immediately upon awakening during a 7-day period. Participants also spent two non-consecutive nights in the sleep laboratory where they were awoken 5 min into each continuous REM sleep stage, upon which they gave a verbal dream report. The content of a total of 151 home and 120 laboratory dream reports was analysed by two blind judges using the modified Differential Emotions Scale. It was found that: (1) home dream reports were more emotional than laboratory early REM dream reports, but not more emotional than laboratory late REM dream reports; (2) home dream reports contained a higher density of emotions than laboratory (early or late REM) dream reports; and (3) home dream reports were more negative than laboratory dream reports, but differences between home and early REM reports were larger than those between home and late REM reports. The results suggest that differences between home and laboratory dream reports in overall emotionality may be due to the time of night effect. Whether differences in the density of emotions and negative emotionality are due to sleep environment or due to different reporting procedures and time spent in a sleep stage, respectively, remains to be determined in future studies.

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