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  • 101.
    Granéli, Cecilia
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Brolén, Gabriella
    Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Global Medicines Development, CVRM, AstraZeneca Gothenburg, Mölndal, Sweden.
    Diabetic Cardiomyopathy Modelling Using Induced Pluripotent Stem Cell Derived Cardiomyocytes: Recent Advances and Emerging Models2019In: Stem Cell Reviews, ISSN 1550-8943, E-ISSN 1558-6804, Vol. 15, no 1, p. 13-22Article in journal (Refereed)
    Abstract [en]

    The global burden of diabetes has drastically increased over the past decades and in 2017 approximately 4 million deaths were caused by diabetes and cardiovascular complications. Diabetic cardiomyopathy is a common complication of diabetes with early manifestations of diastolic dysfunction and left ventricular hypertrophy with subsequent progression to systolic dysfunction and ultimately heart failure. An in vitro model accurately recapitulating key processes of diabetic cardiomyopathy would provide a useful tool for investigations of underlying disease mechanisms to further our understanding of the disease and thereby potentially advance treatment strategies for patients. With their proliferative capacity and differentiation potential, human induced pluripotent stem cells (iPSCs) represent an appealing cell source for such a model system and cardiomyocytes derived from induced pluripotent stem cells have been used to establish other cardiovascular related disease models. Here we review recently made advances and discuss challenges still to be overcome with regard to diabetic cardiomyopathy models, with a special focus on iPSC-based systems. Recent publications as well as preliminary data presented here demonstrate the feasibility of generating cardiomyocytes with a diabetic phenotype, displaying insulin resistance, impaired calcium handling and hypertrophy. However, capturing the full metabolic- and functional phenotype of the diabetic cardiomyocyte remains to be accomplished. 

  • 102.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Visual features and perceptual context modulate attention towards evolutionarily relevant threatening stimuli: Electrophysiological evidence2019In: Emotion, ISSN 1528-3542, E-ISSN 1931-1516, Vol. 19, no 2, p. 348-364Article in journal (Refereed)
    Abstract [en]

    The snake detection hypothesis claims that predatory pressure from snakes has shaped the primate visual system, but we still know very little about how the brain processes evolutionarily important visual cues, and which factors are crucial for quick detection of snakes. We investigated how visual features modulate the electrophysiological markers of early attentional processes. In Experiment 1, we compared snake, rope, gun, and bird images to isolate the effects due to curvilinearity of the stimuli. The results showed that both snake and rope images elicited enhanced P1 and N1 event-related potential components as well as early posterior negativity (EPN). In Experiment 2, we studied whether nonthreatening curvilinear images (i.e., ropes) still elicit the enhanced electrophysiological responses when snake images are not presented as stimuli, and therefore the context does not provoke top-down attention to curvilinear shapes. Rope images still evoked an enhanced EPN, suggesting that curvilinear shapes are preferably captured by attentional processes. However, this effect was smaller than in Experiment 1, in which snake images were present. Thus, our results hint to the possibility that the perceptual context may interact with processing of shape information, drawing attention to curvilinear shapes when the presence of snakes is expectable. Furthermore, we observed that spatial frequency of the visual stimuli modulated especially the early electrophysiological responses, and decreased the differences between stimulus categories in EPN without completely eliminating them. The findings suggest that low-level and high-level mechanisms interact to give an attentional priority to potentially threatening stimuli.

  • 103.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland.
    Castellotti, Serena
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Petrizzo, Irene
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Benedetti, Viola
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Processing of natural scenery is associated with lower attentional and cognitive load compared with urban ones2019In: Journal of Environmental Psychology, ISSN 0272-4944, E-ISSN 1522-9610, Vol. 62, p. 1-11Article in journal (Refereed)
    Abstract [en]

    Environmental psychology has provided evidence for psychologically favorable effects of exposure to natural settings, by means of controlled laboratory experiments as well as outdoor field studies. Most of these studies have employed subjective rating scales to assess processes and outcomes of exposure to nature, while only few of them have used physiological measures to assess the neural correlates of these benefits. The present study used electroencephalography (EEG) to explore how the brain engages in processing of images of natural vs. urban scenery. During EEG recording, the participants (n = 32) were presented with a series of photos depicting urban or natural scenery. Participants rated the sceneries for their subjective relaxing value. Images of natural scenery were rated as more relaxing compared to the images of urban scenery. Event related potentials suggested a lower attentional demand for images of natural scenery compared to urban ones. Signal spectral analyses revealed differences in brain activity level and cognitive demand between natural and urban scenery. Our data suggest that the visual perception of natural environments calls for less attentional and cognitive processing, compared with urban ones. © 2019 Elsevier Ltd

  • 104.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Turku, Finland /Turku Brain and Mind Center, University of Turku, Turku, Finland.
    Souchet, Jérémie
    Station D'Ecologie Théorique et Expérimentale Du CNRS, France.
    Aubret, Fabien
    Station D'Ecologie Théorique et Expérimentale Du CNRS, France.
    Segurini, Giulia V.
    Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Pattern matters: Snakes exhibiting triangular and diamond-shaped skin patterns modulate electrophysiological activity in human visual cortex2019In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 131, p. 62-72Article in journal (Refereed)
    Abstract [en]

    The neural and perceptual mechanisms that support the efficient visual detection of snakes in humans are still not fully understood. According to the Snake Detection Theory, selection pressures posed by snakes on early primates have shaped the development of the visual system. Previous studies in humans have investigated early visual electrophysiological activity in response to snake images vs. various alternative dangerous or non-dangerous stimuli. These studies have shown that the Early Posterior Negativity (EPN) component is selectively elicited by snake or snake-like images. Recent findings yielded the complementary/alternative hypothesis that early humans (and possibly other primates) evolved an aversion especially for potentially harmful triangular shapes, such as teeth, claws or spikes. In the present study we investigated the effect of triangular and diamond-shaped patterns in snake skins on the ERP correlates of visual processing in humans. In the first experiment, we employed pictures of snakes displaying either triangular/diamond-shaped patterns or no particular pattern on their skins, and pictures of frogs as control. Participants observed a random visual presentation of these pictures. Consistent with previous studies, snakes elicited an enhanced negativity between 225 and 300 ms (EPN) compared to frogs. However, snakes featuring triangular/diamond-shaped patterns on their skin produced an enhanced EPN compared to the snakes that did not display such patterns. In a second experiment we used pictures displaying only skin patterns of snakes and frogs. Results from the second experiment confirmed the results of the first experiment, suggesting that triangular snake-skin patterns modulate the activity in human visual cortex. Taken together, our results constitute an important contribution to the snake detection theory. 

  • 105.
    Gustafsson, Erik
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Studies on regulatory networks governing virulence gene transcription in Staphylococcus aureus2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Staphylococcus aureus pathogenicity is dependent on the coordinated action of a number of virulence factors and the expression of these virulence factors is determined by several global regulators. The main regulator seems to be agr but there are several additional regulators (mostly sarA homologues) involved that mainly act downstream of agr. Some of these regulators control virulence gene expression directly but they also regulate each other forming complex regulatory networks. The work described in this thesis aims at better understanding of the function of the agr system and how different regulators act together in controlling transcription of virulence genes.

    Most virulence factors in S. aureus are expressed in a growth phase-dependent manner governed by the auto-inducible quorum sensing system agr. Activation of agr results in rapid increase of the regulator RNAIII and occurs in response to accumulation of the auto-inducing peptide (AIP). In order to activate the agr system a low basal transcription of the agr operon must be assumed. This basal activity of the operon is stimulated by sarA. To be able to study how SarA would affect activation of agr, a mathematical model of the agr system was set up. The model predicted that the agr system is hysteretic, meaning that activation of agr occurs in a switch-like manner at a specific concentration of AIP, whereas it is inactivated at a specific lower concentration of AIP. According to the model, SarA does not seem essential for the function of the agr switch but alters the concentration of AIP (cell density) at which agr is activated. This was supported by Northern blot analysis of RNAIII in S. aureus mutants with different levels of sarA expression.

    To determine how agr and the other regulators act together in controlling transcription of virulence genes, we studied the regulation of one gene (spa) that is negatively regulated by agr and the genes encoding extracellular proteases (aur and sspA), which are positively regulated by agr. To analyze the general principles of how each component in a regulatory system contributes to expression of a virulence gene, a mathematical model of the regulation of spa (protein A) transcription was developed.

    Parameter values in this mathematical model were determined by fitting the output of the model to quantitative Northern blot data from various S. aureus regulatory mutants using a gradient search method. The model was validated by correctly predicted spa expression levels in different regulatory mutants not included in the parameter value search. The mathematical model revealed that Rot and SarS act synergistically to stimulate spa expression and that sarA and sarS seem to balance each other in a way that when the activating impact of sarS is small, e.g. in the wild type, the repressive impact of sarA is small, while in a agr-deficient background, when the impact of sarS is maximal, the repressive effect of sarA is close to its maximum.

    Previous studies have shown that SarR down-regulates transcription of sarA, which is a repressor of the aur and sspA transcription. This means that inactivation of sarR would result in decreased transcription of aur and sspA, which was confirmed by mRNA analysis using quantitative real-time PCR. However, we also found that sarR acted as a direct stimulator of aur and sspA transcription and that sarR is required for maximal transcription of aur and sspA.

  • 106.
    Gustafsson, Erik
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde.
    Nilsson, Patric
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Enroth, Helena
    Department of Clinical Microbiology, Skaraborg Hospital, Capio Diagnostic AB, Skövde.
    Beronius, Marie Kia
    Centre for General Medicine, Kungsbacka.
    Andersson, Rune
    6Research and Development Centre, Skaraborg Hospital, Skövde, Sweden.
    Arvidson, Staffan
    Department of Microbiology, Tumour and Cell Biology (MTC), Karolinska Institutet, Stockholm.
    Invasive Staphylococcus aureus strains are highly variable in PFGE patterns, agr group and exoprotein production2009In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 41, no 8, p. 577-583Article in journal (Refereed)
    Abstract [en]

    In the present study, we have investigated 37 invasive Staphylococcus aureus strains (collected between 1997 and 2005) from 33 human episodes of septicaemia causing either endocarditis or vertebral osteomyelitis. All S. aureus strains were typed using pulsed field gel electrophoresis (PFGE), and most strains belonged to any of 4 different PFGE clusters. There was no correlation between any of the PFGE clusters with site of infection. All strains showed highly different expression patterns of extracellular proteins, i.e. we found a vast variation in the number of proteins and amount of individual proteins expressed by the different strains. There was no correlation between any cluster of exoprotein patterns with endocarditis or with vertebral osteomyelitis. We did not find any correlation between agr group and endocarditis, as previously reported. On the other hand, a correlation between some of the PFGE clusters with a certain agr group was found. Known risk factors for S. aureus infections were observed in a majority of the patients.

  • 107.
    Gustavsson, Ann
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Jonsson, Annie
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Rumslig fördelning av juvenila och adulta stormusslor: Metodstudie i sjöaroch vattendrag med god eller dålig föryngring2010Report (Other (popular science, discussion, etc.))
  • 108.
    Götmark, Frank
    et al.
    Göteborgs universitet.
    Nordén, Björn
    Göteborgs universitet.
    Franc, Niklas
    Göteborgs universitet.
    Paltto, Heidi
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    von Proschwitz, Ted
    Naturhistoriska Riksmuseet.
    Økland, Bjørn
    Norwegian Forest and Landscape Institute.
    Jensen, Anna Monrad
    Sveriges Lantbruksuniversitet.
    Naturvårdsgallring: vad är det?2009In: Biodiverse, ISSN 1401-5064, Vol. 14, no 1, p. 20-20Article in journal (Other (popular science, discussion, etc.))
  • 109.
    Handlin, Linda
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Human-Human and Human-Animal Interaction: Some Common Physiological and Psychological Effects2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the present thesis was to investigate hormonal and physiological effects in mothers during a breastfeeding session and in dogs and their owners in response to short-term interaction.In study one, sixty-six mothers receiving either exogenous oxytocin infusion and/or epidural analgesia (EDA) during labor or intramuscular oxytocin injection post partum were studied. Oxytocin, prolactin, adrenocorticotrophic hormone (ACTH) and cortisol levels, as well as blood pressure were measured during a breastfeeding session two days after birth. In response to breastfeeding two days after birth, the mothers displayed a pulsatile release of oxytocin and increasing prolactin levels. In addition, the activity in the HPA-axis was reduced and maternal blood pressure decreased. The results also show that EDA administration in combination with oxytocin during labor resulted insignificantly lower oxytocin levels and higher cortisol levels, as well as higher bloodpressure in response to breastfeeding two days after birth, compared to EDA administration alone. In addition, oxytocin infusions dose-dependently lowered the mothers’ endogenous oxytocin levels two days after birth. In study two, ten female dog owners and their male Labrador dogs participated, together with ten controls. Their levels of oxytocin, cortisol and insulin, as well as their heart rate, were measured. The connection between the quality of the dogowner relationship and hormone levels was also explored. Short-term interaction between dogs and their owners resulted in oxytocin release in both species and their cortisol levels and heart rate were also affected. Oxytocin levels and positive attitudes regarding the dog-owner relationship were positively correlated. In conclusion, both human-human and human-animal interactions induce oxytocin release and promote oxytocin mediated effects, such as decreasing cortisol levels and blood pressure. In addition, social interaction and oxytocin levels arepositively related.

  • 110.
    Handlin, Linda
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Hydbring-Sandberg, Eva
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden .
    Nilsson, Anne
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, Skara, Sweden .
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Göteborgs universitet.
    Jansson, Anna
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, S-75007 Uppsala, Sweden.
    Uvnäs-Moberg, Kerstin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Short-Term Interaction between Dogs and Their Owners: Effects on Oxytocin, Cortisol, Insulin and Heart Rate-An Exploratory Study2011In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 24, no 3, p. 301-315Article in journal (Refereed)
    Abstract [en]

    The aim of this exploratory study was to determine heart rate and the levels of oxytocin, cortisol, and insulin in dogs and their owners in response to a short-term interaction. In addition, the dogs' behavior was studied. The owners' responses were compared with those obtained from a control group. Ten female volunteers and their own male Labrador dogs participated in an experiment during which the owner stroked, petted, and talked with her dog during the first 3 minutes. Blood samples were collected from both dog and owner before (0) and at 1, 3, 5, 15, 30, and 60 minutes after the start of the interaction. Blood samples were analyzed by EIA. Heart rate was monitored telemetrically. The data were analyzed using linear mixed models and paired t-tests. The dogs' oxytocin levels were significantly increased 3 minutes after the start of the interaction (p = 0.027). Cortisol levels were significantly increased after 15 and 30 minutes (p = 0.004 and p = 0.022, respectively), and heart rate was significantly decreased after 55 minutes (p = 0.008). The dogs displayed normal behaviors during the experiment. The owners' oxylocin levels peaked between 1 and 5 minutes after interaction (p = 0.026). No such effect was seen in the controls. Cortisol levels displayed a significant decrease at 15 or 30 minutes in both owners and controls, and insulin levels did so at 60 minutes (p = 0.030, p = 0.002 and p = 0.002, p < 0.0001, respectively). Heart rate decreased significantly in the owners at 55 and 60 minutes (p = 0.0008) but not in the controls. In conclusion, short-term sensory interaction between dogs and their owners influences hormonal levels and heart rate. However, further studies need to be performed in order to better understand the effects of interaction between dogs and their owners.

  • 111.
    Handlin, Linda
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences. Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Jonas, Wibke
    Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Petersson, Maria
    Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska University Hospital/Karolinska Institute, Stockholm, Sweden.
    Ejdebäck, Mikael
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Ransjö-Arvidsson, Anna-Berit
    Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Nissen, Eva
    University of Skövde, School of Life Sciences. Department of Women and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institute, Stockholm, Sweden.
    Uvnäs-Moberg, Kerstin
    University of Skövde, School of Life Sciences. Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Effects of Sucking and Skin-to-Skin Contact on Maternal ACTH and Cortisol Levels During the Second Day Postpartum - Influence of Epidural Analgesia and Oxytocin in the Perinatal Period2009In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 4, no 4, p. 207-220Article in journal (Refereed)
    Abstract [en]

    Background and Aims: In this study we made a detailed analysis of the mothers' release pattern of adreno-corticotropic hormone (ACTH) and cortisol during a breastfeeding session during the second day postpartum and related these patterns to maternal oxytocin levels as well to the duration of sucking and the duration of skin-to-skin contact before sucking the breast. Furthermore, we investigated if epidural analgesia and oxytocin administration during and after labor influenced the release pattern of ACTH and cortisol.

    Methods: Sixty-three primiparae were included in the study. Fourteen received oxytocin intramuscularly postpartum, nine received oxytocin infusion, 14 received epidural analgesia combined with oxytocin infusion, and six received epidural analgesia alone. Twenty mothers did not receive any of these medical interventions. Blood samples were analyzed for ACTH and cortisol by enzyme-linked immunoassay.

    Results: Both ACTH and cortisol levels fell significantly during the breastfeeding session. A significant negative relationship was found between oxytocin and ACTH levels, but not between oxytocin and cortisol levels. A contact before onset of sucking was significantly and negatively associated with lower cortisol levels, but not with ACTH levels. Cortisol levels differed significantly between mothers having received epidural analgesia with and without oxytocin.

    Conclusions: Breastfeeding is associated with a decrease of ACTH and cortisol levels. Skin-to-skin contact contributes to this effect. ACTH correlated negatively with the duration of sucking and median oxytocin levels, whereas cortisol levels correlated inversely with the duration of skin-to-skin contact preceding sucking, suggesting a partial dissociation between the mechanisms regulating ACTH and cortisol release. In addition, medical interventions in connection with birth influence the activity of the hypothalamic-pituitary-adrenal axis 2 days after birth.

  • 112.
    Handlin, Linda
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Jonas, Wibke
    Karolinska Institute.
    Ransjö-Arvidson, Anna-Berit
    Karolinska Institute.
    Petersson, Maria
    Karolinska University Hospital.
    Uvnäs-Moberg, Kerstin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nissen, Eva
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Influence of Common Birth Interventions on Maternal Blood Pressure Patterns During Breastfeeding 2 Days After Birth2012In: Breastfeeding Medicine, ISSN 1556-8253, Vol. 7, no 2, p. 93-99Article in journal (Refereed)
    Abstract [en]

    Objective: This study investigated possible influences of medical interventions during labor on maternal blood pressure during a breastfeed 2 days postpartum.

    Subjects and Methods: Sixty-six primiparae with normal deliveries were consecutively recruited. Blood pressure was measured at –5, 10, 30, and 60 minutes during a morning breastfeed 2 days postpartum. Five treatment groups were formed based on the medical interventions received during labor: Non-medicated mothers (Control group, n=21); mothers receiving epidural analgesia (EDA) with oxytocin (OT) stimulation (EDAOT group, n=14); mothers receiving EDA without OT stimulation (EDAnon-OT group, n=7); mothers receiving OT stimulation only (OT intravenously [iv] group, n=9); and mothers receiving 10 IU of OT intramuscularly (im) only (OT im group, n=15).

    Results: Baseline diastolic, but not systolic, blood pressure differed between the groups as displayed by significantly lower diastolic blood pressure in the EDAnon-OT group compared with the Control group, the OT iv group, and the EDAOT group (p=0.045, p=0.041, and p=0.024, respectively). Both systolic and diastolic blood pressure fell significantly during the breastfeeding session in the Control group (p=0.001 and p=0.004, respectively), the OT im group (p=0.006 and p=0.001, respectively), and the EDAOT group (p=0.028 and p=0.002, respectively), and the fall in diastolic blood pressure tended to be significant in the OT iv group (p=0.050). The duration of skin-to-skin contact before breastfeeding correlated positively with the decrease in systolic blood pressure in the OT im group (Rs=0.540, p=0.046).

    Conclusion: Administration of EDA during labor lowers baseline diastolic blood pressure and abolishes the fall in blood pressure in response to a breastfeed 2 days after birth.

  • 113.
    Handlin, Linda
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Nilsson, Anne
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Hydbring-Sandberg, Eva
    University of Agricultural Sciences, Uppsala.
    Uvnäs-Moberg, Kerstin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Associations between the Psychological Characteristics of the Human-Dog Relationship and Oxytocin and Cortisol Levels2012In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 25, no 2, p. 215-228Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore possible correlations between dog owners' relationships with their dogs, as measured with the Monash Dog Owner Relationship Scale (MDORS), and oxytocin and cortisol levels in both the owners and their dogs. Ten female owners of male Labrador Retrievers completed the MDORS. The scores obtained from the single items, subscales, and total score of the MDORS were calculated. Ten blood samples were collected from each dog owner and her dog during a 60-minute interaction. Blood samples were analyzed for oxytocin and cortisol by Enzyme Immuno Assay (EIA) and mean values of oxytocin and cortisol were calculated in both owners and dogs. The MDORS scores obtained were correlated with basal and mean oxytocin and cortisol levels. The correlation analysis revealed some relationships between the scores of items in the MDORS that reflect the character of the dog-owner-relationship and the owners' hormone levels. For example, higher oxytocin levels in the owners were associated with greater frequency in kissing their dogs (rs = 0.864, p = 0.001). Lower cortisol levels in the owners were associated with their perception that it will be more traumatic when their dog dies (rs = -0.730, p = 0.025). The correlation analysis also revealed some relationships between the scores of items in the MDORS and the dogs' hormone levels. For example, greater frequency in owners kissing their dogs was associated with higher oxytocin levels in the dogs (rs = 0.753, p = 0.029). Six items in the subscale Perceived Costs, as well as the subscale itself, correlated significantly with the dogs' oxytocin levels (rs = 0.820, p = 0.007), that is, the lower the perceived cost, the higher the dogs' oxytocin levels. In addition, significant correlations between the oxytocin levels of the owners and the dogs were demonstrated. Possible mechanisms behind these correlations are discussed. In conclusion, the scores of some items and the subscales of the MDORS correlated with oxytocin, and to a lesser extent cortisol, levels in both the owners and dogs.

  • 114.
    Hedberg Oldfors, Carola
    et al.
    Sahlgrenska Academy, University of Gothenburg.
    Garcia Dios, Diego
    Sahlgrenska Academy, University of Gothenburg.
    Linder, Anna
    Sahlgrenska Academy, University of Gothenburg.
    Visuttijai, Kittichate
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Sahlgrenska Academy, University of Gothenburg.
    Samuelson, Emma
    Sahlgrenska Academy, University of Gothenburg.
    Karlsson, Sandra
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nilsson, Staffan
    Chalmers University of Technology.
    Behboudi, Afrouz
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Analysis of an independent tumor suppressor locus telomeric to Tp53 suggested Inpp5k and Myo1c as novel tumor suppressor gene candidates in this region2015In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 16, no 1, article id 80Article in journal (Refereed)
    Abstract [en]

    Several reports indicate a commonly deleted chromosomal region independent from, and distal to the TP53 locus in a variety of human tumors. In a previous study, we reported a similar finding in a rat tumor model for endometrial carcinoma (EC) and through developing a deletion map, narrowed the candidate region to 700 kb, harboring 19 genes. In the present work real-time qPCR analysis, Western blot, semi-quantitative qPCR, sequencing, promoter methylation analysis, and epigenetic gene expression restoration analyses (5-aza-2'-deoxycytidine and/or trichostatin A treatments) were used to analyze the 19 genes located within the candidate region in a panel of experimental tumors compared to control samples.

    RESULTS:

    Real-time qPCR analysis suggested Hic1 (hypermethylated in cancer 1), Inpp5k (inositol polyphosphate-5-phosphatase K; a.k.a. Skip, skeletal muscle and kidney enriched inositol phosphatase) and Myo1c (myosin 1c) as the best targets for the observed deletions. No mutation in coding sequences of these genes was detected, hence the observed low expression levels suggest a haploinsufficient mode of function for these potential tumor suppressor genes. Both Inpp5k and Myo1c were down regulated at mRNA and/or protein levels, which could be rescued in gene expression restoration assays. This could not be shown for Hic1.

    CONCLUSION:

    Innp5k and Myo1c were identified as the best targets for the deletions in the region. INPP5K and MYO1C are located adjacent to each other within the reported independent region of tumor suppressor activity located at chromosome arm 17p distal to TP53 in human tumors. There is no earlier report on the potential tumor suppressor activity of INPP5K and MYO1C, however, overlapping roles in phosphoinositide (PI) 3-kinase/Akt signaling, known to be vital for the cell growth and survival, are reported for both. Moreover, there are reports on tumor suppressor activity of other members of the gene families that INPP5K and MYO1C belong to. Functional significance of these two candidate tumor suppressor genes in cancerogenesis pathways remains to be investigated.

  • 115.
    Hedelin, Hans
    et al.
    Skaraborgs sjukhus.
    Jonsson, Karin
    Skaraborgs sjukhus.
    Lundh, Dan
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Pain associated with the chronic pelvic pain syndrome is strongly related to the ambient temperature2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 4, p. 279-283Article in journal (Refereed)
    Abstract [en]

    Objective. There are indications suggesting that the pain associated with the chronic pelvic pain syndrome (CPPS) may be related to cold. The purpose of the present study was to evaluate how the symptom intensity reported by the patient relates to the time of the year in a temperate climate, i.e. to the ambient temperature and to weather changes. Material and methods. Thirty-one patients, mean age 51 years (range 35–66 years), with CPPS for 17 ± 10 years (3–42 years) were asked to complete a set of questionnaires including questions concerning how they experienced their symptom intensity during the different seasons using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire. Results. The total NIH-CPSI score was 22.2 ± 8.2. There was a highly marked relationship between season and pain intensity as reported by the informants: it was experienced to be three times more intense during the winter months. All subjects reported that a temperature drop was associated with deterioration. Conclusion. The strong relationship between the ambient temperature, a drop in temperature and the pain experienced by men with CPPS confirms the association between cold and symptom intensity in the Scandinavian countries, where the seasonal temperature variation spans a long range and the winters are long. The cause of this relationship is still to be established. Muscular spasm/stiffness is a possibility that remains to be explored.

  • 116.
    Heerspink, Hiddo J. L.
    et al.
    Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, Netherlands.
    Sjöström, C. David
    AstraZeneca, Gothenburg, Sweden.
    Inzucchi, Silvio E.
    Section of Endocrinology, Yale University School of Medicine, New Haven, CT, United States.
    Hallow, Melissa K.
    Department of Epidemiology and Biostatistics, University of Georgia School of Public Health, Athens, GA, United States.
    Cain, Valerie A.
    Bogier Clinical and IT Solutions, Inc., Raleigh, NC, United States.
    Rossing, Peter
    Steno Diabetes Center Copenhagen, Gentofte, Denmark / Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
    Stefansson, Bergur V.
    AstraZeneca, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca, Gothenburg, Sweden.
    Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers2019In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 21, no 3, p. 720-725Article in journal (Refereed)
    Abstract [en]

    The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was −71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined. 

  • 117.
    Helldin, Tove
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    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.
    Towards a Clinical Support System for the Early Diagnosis of Sepsis2017In: Digital Human Modeling - Applications in Health, Safety, Ergonomics, and Risk Management: Health and Safety: 8th International Conference, DHM 2017 Held as Part of HCI International 2017 Vancouver, BC, Canada, July 9–14, 2017, Proceedings, Part II / [ed] Vincent G. Duffy, Springer, 2017, p. 23-35Conference paper (Refereed)
    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.

  • 118.
    Hemeren, Paul
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Johannesson, Mikael
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Lebram, Mikael
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Eriksson, Fredrik
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Ekman, Kristoffer
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Veto, Peter
    University of Skövde, The Informatics Research Centre. University of Skövde, School of Informatics.
    The Use of Visual Cues to Determine the Intent of Cyclists in Traffic2014In: 2014 IEEE International Inter-Disciplinary Conference on Cognitive Methods in Situation Awareness and Decision Support (CogSIMA), IEEE Press, 2014, p. 47-51Conference paper (Refereed)
    Abstract [en]

    The purpose of this research was to answer the following central questions: 1) How accurate are human observers at predicting the behavior of cyclists as the cyclists approached a crossing? 2) If the accuracy is reliably better than chance, what cues were used to make the predictions? 3) At what distance from the crossing did the most critical cues occur? 4) Can the cues be used in a model that can reliably predict cyclist intent? We present results that show a number of indicators that can be used in to predict the intention of a cyclist, i.e., future actions of a cyclist, e.g., “left turn” or “continue forward” etc.

    Results of empirical studies show that humans are reasonably good at this type of prediction for a majority of the situations studied. However, some situations seem to contain conflicting information. The results also suggested that human prediction of intention is to a large extent relying on a single “strong” indicator, e.g., that the cyclist makes a clear “head movement”. Several “weaker" indicators that together could be a strong “combined indicator”, or equivalently strong evidence, is likely to be missed or too complex to be handled by humans in real-time. We suggest this line of research can be used to create decision support systems that predict the behavior of cyclists in traffic.

  • 119.
    Hemeren, Paul
    et al.
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Informatics Research Centre.
    Johannesson, Mikael
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Informatics Research Centre.
    Lebram, Mikael
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Informatics Research Centre.
    Eriksson, Fredrik
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Informatics Research Centre.
    Ekman, Kristoffer
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre.
    Veto, Peter
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Informatics Research Centre.
    URBANIST: Signaler som används för att avläsa cyklisters intentioner i trafiken2013Report (Other academic)
    Abstract [sv]

    Genom att titta på ett fåtal bestämda signaler kan man med god träffsäkerhet förutsäga cyklisters beteende, vilket tyder på att de identifierade signalerna är betydelsefulla. Vetskapen om dessa kan, bland annat, praktiskt användas för att utveckla enkla hjälpmedel – såsom medveten placering av fluorescerande eller reflekterande material på leder och/eller införande av olikfärgade hjälmsidor. Dylika kan förväntas förstärka kommunikationen av viktiga signaler. Vetskapen kan även användas för att utbilda oerfarna bilförare. Båda fallen kan i förlängningen ge en säkrare trafikmiljö för oskyddade trafikanter.

  • 120.
    Hiltunen, Seppo
    et al.
    University of Helsinki, Finland.
    Virta, Maarit
    University of Helsinki, Finland.
    Kallio, Sakari
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Finland.
    Paavilainen, Petri
    University of Helsinki, Finland.
    The effects of hypnosis and hypnotic suggestions on the mismatch negativity in highly hypnotizable subjects2019In: International journal of clinical and experimental hypnosis, ISSN 0020-7144, E-ISSN 1744-5183, Vol. 67, no 2, p. 192-216Article in journal (Refereed)
    Abstract [en]

    The neural mechanisms associated with hypnosis were investigated in a group of 9 high hypnotizable subjects by measuring the mismatch negativity (MMN) component of the auditory eventrelated potential (ERP). ERPs were recorded using a passive oddball paradigm to sinusoidal standard and deviant tone stimuli of 500 and 520 Hz, respectively, in four conditions: prehypnosis, neutral hypnosis, hypnotic suggestion for altering the tone perception, and posthypnotic conditions. Earlier studies have indicated that hypnosis and hypnotic suggestions might have an effect on MMN, but the results of our study contradict these results: No statistically significant differences were found between the conditions in the MMN amplitudes.

  • 121.
    Hinrichsen, Hans-Harald
    et al.
    Dept. Evolutionary Ecology, Kiel, Germany.
    Large, Scott
    International Council for the Exploration of the Sea (ICES), Copenhagen, Denmark.
    Möllmann, Christian
    University of Hamburg, Institute of Hydrobiology and Fishery Science, Hamburg, Germany.
    Müller-Karulis, Bärbel
    Stockholm University, Baltic Sea Centre, Stockholm, Sweden.
    Neuenfeldt, Stefan
    Technical University of Denmark, National Institute of Aquatic Resources, Section for Marine Ecology and Oceanography, Charlottenlund, Denmark.
    Norrström, Niclas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Schmidt, Jörn
    Christian-Albrechts-Universität zu Kiel, Department of Economics, Kiel, Germany.
    Sguotti, Camilla
    Institute for Hydrobiology and Fisheries Science, University of Hamburg, Hamburg, Germany.
    Tomczak, Maciej
    Stockholm University, Baltic Sea Centre, Stockholm, Sweden.
    Voss, Rudi
    Christian-Albrechts-Universität zu Kiel, Department of Economics, Kiel, Germany.
    Hamrén, Henrik
    Stockholm University, Baltic Sea Centre, Stockholm, Sweden.
    Report of the Workshop on DEveloping Integrated AdviCE for Baltic Sea ecosystem-based fisheries management (WKDEICE): 18-21 April 2016 Helsinki, Finland2016Report (Other academic)
    Abstract [en]

    The first ICES Workshop on DEveloping Integrated AdviCE for Baltic Sea ecosystem-based fisheries management (WKDEICE) had the aim to start identifying and devel-oping ways to include environmental and economic considerations into ICES advice on Baltic Sea fish stocks. The WKDEICE meeting was held in Helsinki, Finland, on18–21 April 2016, with 12 participants from three countries and was chaired by Chris-tian Möllmann (Germany), Rudi Voss (Germany), and Maciej T. Tomczak (Sweden). Focusing on Eastern Baltic cod (subdivisions 25-32), WKDEICE addressed five main topics:

    1)developing a strategy for integrating environmental and economic infor-mation in fish stock advice;

    2)conducting an integrated environmental assessment;

    3)conducting a socio-economic assessment;

    4)conducting short-term projections informed by environmental and economic conditions; and

    5)communicating the approach and the results.

    Eastern Baltic cod has been selected as a case study. The exercise will likely be ex-tended to the baltic clupeid stocks of herring and sprat.

    A central point of the meeting was to discuss and design a concept of operationalized Integrated Ecosystem Assessment (IEA) including short-term predictions, to be used in advice on the main Baltic Sea fish stocks. The group developed an operational strategy, and started to quantify potentially useful environmental indicators, focusing on hydrographic conditions influencing cod recruitment. Economic short-term fore-casts were established to include the human dimension, and to provide additional quantitative information on fishing options. The suggested integrated advice frame-work will be further developed using simulation modelling during a next meeting in 2017. This meeting will be coordinated with the ICES/HELCOM Working Group on Integrated Assessments of the Baltic Sea (WGIAB) and the Baltic Fisheries Assess-ment Working Group (WGBFAS) to test concepts, apply Management Strategy Eval-uation (MSE) models, and have direct feedback for relevant ICES bodies. 

  • 122.
    Holmgren, Gustav
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Ghosheh, Nidal
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry/Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Zeng, Xianmin
    Buck Institute for Research on Aging, Buck Institute, Novato, California, USA.
    Bogestål, Yalda
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca Research and Development, Global Medicines Development, Cardiovascular and Metabolic Diseases Global Medicines Development Unit, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Identification of stable reference genes in differentiating human pluripotent stem cells2015In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 47, no 6, p. 232-239Article in journal (Refereed)
    Abstract [en]

    Reference genes, often referred to as housekeeping genes (HKGs), are frequently used to normalize gene expression data based on the assumption that they are expressed at a constant level in the cells. However, several studies have shown that there may be a large variability in the gene expression levels of HKGs in various cell types. In a previous study, employing human embryonic stem cells (hESCs) subjected to spontaneous differentiation, we observed that the expression of commonly used HKG varied to a degree that rendered them inappropriate to use as reference genes under those experimental settings. Here we present a substantially extended study of the HKG signature in human pluripotent stem cells (hPSC), including nine global gene expression datasets from both hESC and human induced pluripotent stem cells (hiPSCs), obtained during directed differentiation towards endoderm-, mesoderm-, and ectoderm derivatives. Sets of stably expressed genes were compiled and a handful of genes (e.g., EID2, ZNF324B, CAPN10, and RABEP2) were identified as generally applicable reference genes in hPSCs across all cell lines and experimental conditions. The stability in gene expression profiles was confirmed by quantitative PCR (RT-qPCR) analysis. Taken together, the current results suggest that differentiating hPSCs have a distinct HKG signature, which in some aspects is different from somatic cell types, and underscore the necessity to validate the stability of reference genes under the actual experimental setup used. In addition, the novel putative HKGs identified in this study can preferentially be used for normalization of gene expression data obtained from differentiating hPSCs.

  • 123.
    Holmgren, Gustav
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden / Takara Bio Europe AB, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca Gothenburg, CVMD GMed, GMD, Mölndal, Sweden.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Lindahl, Anders
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Expression profiling of human pluripotent stem cell-derived cardiomyocytes exposed to doxorubicin - integration and visualization of multi omics data2018In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 163, no 1, p. 182-195Article in journal (Refereed)
    Abstract [en]

    Anthracyclines, such as doxorubicin, are highly efficient chemotherapeutic agents against a variety of cancers. However, anthracyclines are also among the most cardiotoxic therapeutic drugs presently on the market. Chemotherapeutic-induced cardiomyopathy is one of the leading causes of disease and mortality in cancer survivors. The exact mechanisms responsible for doxorubicin-induced cardiomyopathy are not completely known, but the fact that the cardiotoxicity is dose-dependent and that there is a variation in time-to-onset of toxicity, and gender- and age differences suggests that several mechanisms may be involved.In the present study, we investigated doxorubicin-induced cardiotoxicity in human pluripotent stem cell-derived cardiomyocytes using proteomics. In addition, different sources of omics data (protein, mRNA, and microRNA) from the same experimental setup were further combined and analyzed using newly developed methods to identify differential expression in data of various origin and types. Subsequently, the results were integrated in order to generate a combined visualization of the findings.In our experimental model system, we exposed cardiomyocytes derived from human pluripotent stem cells to doxorubicin for up to two days, followed by a wash-out period of additionally 12 days. Besides an effect on the cell morphology and cardiomyocyte functionality, the data show a strong effect of doxorubicin on all molecular levels investigated. Differential expression patterns that show a linkage between the proteome, transcriptome, and the regulatory microRNA network, were identified. These findings help to increase the understanding of the mechanisms behind anthracycline-induced cardiotoxicity and suggest putative biomarkers for this condition.

  • 124.
    Holmgren, Gustav
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Sjögren, Anna-Karin
    Department of Discovery Safety, Drug Safety and Metabolism, AstraZeneca RandD, Mölndal, Sweden.
    Barragan, Isabel
    Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Sabirsh, Alan
    Department of Bioscience, Cardiovascular and Metabolic Diseases, AstraZeneca RandD, Mölndal, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Cellectis AB, Gothenburg, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Björquist, Petter
    NovaHep AB, Gothenburg, Sweden / Cellectis AB, Gothenburg, Sweden.
    Ingelman-Sundberg, Magnus
    Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Tommy B.
    Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Drug Metabolism and Pharmacokinetics, AstraZeneca RandD, Mölndal, Sweden.
    Edsbagge, Josefina
    Cellectis AB, Gothenburg, Sweden.
    Long-term chronic toxicity testing using human pluripotent stem cell-derived hepatocytes2014In: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 42, no 9, p. 1401-1406Article in journal (Refereed)
    Abstract [en]

    Human pluripotent stem cells (hPSC) have the potential to become important tools for the establishment of new models for in vitro drug testing of, for example, toxicity and pharmacological effects. Late-stage attrition in the pharmaceutical industry is to a large extent caused by selection of drug candidates using nonpredictive preclinical models that are not clinically relevant. The current hepatic in vivo and in vitro models show clear limitations, especially for studies of chronic hepatotoxicity. For these reasons, we evaluated the potential of using hPSC-derived hepatocytes for long-term exposure to toxic drugs. The differentiated hepatocytes were incubated with hepatotoxic compounds for up to 14 days, using a repeated-dose approach. The hPSC-derived hepatocytes became more sensitive to the toxic compounds after extended exposures and, in addition to conventional cytotoxicity, evidence of phospholipidosis and steatosis was also observed in the cells. This is, to the best of our knowledge, the first report of a long-term toxicity study using hPSC-derived hepatocytes, and the observations support further development and validation of hPSC-based toxicity models for evaluating novel drugs, chemicals, and cosmetics.

  • 125.
    Holmgren, Gustav
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Lindahl, Anders
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca Gothenburg, CVMD GMed, GMD, Mölndal, Sweden.
    MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity2016In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 34, p. 26-34Article in journal (Refereed)
    Abstract [en]

    Anthracyclines, such as doxorubicin, are well-established, highly efficient anti-neoplastic drugs used for treatment of a variety of cancers, including solid tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin has, however, been hampered by severe cardiotoxic side-effects. In order to prevent or reverse negative side-effects of doxorubicin, it is important to find early biomarkers of heart injury and drug-induced cardiotoxicity. The high stability under extreme conditions, presence in various body fluids, and tissue-specificity, makes microRNAs very suitable as clinical biomarkers. The present study aimed towards evaluating the early and late effects of doxorubicin on the microRNA expression in cardiomyocytes derived from human pluripotent stem cells. We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a, miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are differentially expressed upon, and after, treatment with doxorubicin. Investigation of the biological relevance of the identified microRNAs revealed connections to cardiomyocyte function and cardiotoxicity, thus supporting the findings of these microRNAs as potential biomarkers for drug-induced cardiotoxicity.

  • 126.
    Holmgren, Gustav
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Bogestål, Yalda
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. SP Chemistry Materials and Surfaces, Gothenburg, Sweden.
    Améen, Caroline
    Takara Bio Europe AB (former Cellectis AB), Gothenburg, Sweden.
    Åkesson, Karolina
    Takara Bio Europe AB (former Cellectis AB), Gothenburg, Sweden.
    Holmgren, Sandra
    Takara Bio Europe AB (former Cellectis AB), Gothenburg, Sweden.
    Lindahl, Anders
    Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Takara Bio Europe AB (former Cellectis AB), Gothenburg, Sweden / GMed CVMD, AstraZeneca, Mölndal.
    Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells2015In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 328, p. 102-111Article in journal (Refereed)
    Abstract [en]

    Doxorubicin is a chemotherapeutic agent indicated for the treatment of a variety of cancer types, including leukaemia, lymphomas, and many solid tumours. The use of doxorubicin is, however, associated with severe cardiotoxicity, often resulting in early discontinuation of the treatment. Importantly, the toxic symptoms can occur several years after the termination of the doxorubicin administration. In this study, the toxic effects of doxorubicin exposure have been investigated in cardiomyocytes derived from human embryonic stem cells (hESC). The cells were exposed to different concentrations of doxorubicin for up to 2 days, followed by a 12 day recovery period. Notably, the cell morphology was altered during drug treatment and the cells showed a reduced contractile ability, most prominent at the highest concentration of doxorubicin at the later time points. A general cytotoxic response measured as Lactate dehydrogenase leakage was observed after 2 days' exposure compared to the vehicle control, but this response was absent during the recovery period. A similar dose-dependant pattern was observed for the release of cardiac specific troponin T (cTnT) after 1 day and 2 days of treatment with doxorubicin. Global transcriptional profiles in the cells revealed clusters of genes that were differentially expressed during doxorubicin exposure, a pattern that in some cases was sustained even throughout the recovery period, suggesting that these genes could be used as sensitive biomarkers for doxorubicin-induced toxicity in human cardiomyocytes. The results from this study show that cTnT release can be used as a measurement of acute cardiotoxicity due to doxorubicin. However, for the late onset of doxorubicin-induced cardiomyopathy, cTnT release might not be the most optimal biomarker. As an alternative, some of the genes that we identified as differentially expressed after doxorubicin exposure could serve as more relevant biomarkers, and may also help to explain the cellular mechanisms behind the late onset apoptosis associated with doxorubicin-induced cardiomyopathy.

  • 127.
    Holmgren, Noel M. A.
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Norrström, Niclas
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Getz, Wayne M.
    Artificial neural networks in models of specialisation, guild evolution and sympatric speciation2010In: Modelling Perception in Artificial Neural Networks / [ed] Colin R. Tosh & Graeme D. Ruxton, Cambridge University Press, 2010, p. 236-254Chapter in book (Other academic)
  • 128.
    Holmgren, Noél M. A.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    MSY analyses for herring and sprat in the Baltic Sea, methods and suggested reference points2011In: ICES report of the Baltic Fisheries Assessment working Group (WGBFAS), Copenhagen: ICES , 2011, p. 798-804Chapter in book (Other academic)
    Abstract [en]

    The concept of maximum sustainable yield (MSY) rests on the notion that an intermediately sized stock exists at which the biomass production is at its maximum. the maximum is a result of density-dependent negative feedback on percapita production with increasing stock size. the harvesting is sustainable if it equals the stock productivity. the stock productivity depends on environmental variables, typically food-availability but also temperature and salinity may be important. Predation does not affect the productivity directly, but it is important to consider how the annual surplus production is shared with predators and hence affects the fishing yield. In the stock model we use for MSY analyses we differentiate between internal factors affecting density-dependence and external factors that either drive productivity or represent predation.

    To estimate MSY reference points we modelled some stocks with Monte-Carlo simulations (see WD6 for details). The stochastic properties of the stock are estimated and implemented in the stochastic behaviour of the model in order to find the natural range of stock ariables under MSY management. This can be a basis for B trigger in ICES framework, the SSB at which the F MSY is re-evaluated or an adjusted F is adopted according to the harvest control rule. Under some conditions, stochastic simulations will have F MSY that are different from deterministic runs, i e yields are asymmetrical around their means.

    The stock model has two variables, NAA (numbers at age) and WAA (weight at age). The functions and their parameters to update the variables annually were obtained from statistical analyses of the data and results from XSA runs provided by the WGBFAS stock coordinators. Four functions were estimated statistically:1) Number of recruits per SSB as a linear function of SSB2) Age-specific natural mortality as a linear function of predator abundance ( e. g. Cod SSB)3) Weight of recruits as a linear function of average parent weight4) Average weight increase as a linear function of WAA and year-specific growthThe MS errors of the regressions were used as variances of the normal distributions from which a random parameter was generated. If body growth is negatively correlated with weight it indicates a Von Bertalanffy type of growth. Also, if number of recruits per SSB is negatively correlated with SSB, there is a density-dependence required for a maximum production to exist.

    There are also two external variables that affect the analyses: predator abundance and year-specific growth (named year-growth). The year-growth is a statistical variable tha t encapsulates all year-specific growth common for all age-classes. The year-growth is externally linked driver for variation in productivity of the stock. A Fourier function including the four longest wave-lengths was fitted to the predator abundance and the year-growth respectively. The Fourier functions were representing long term changes in the external conditions, and the residuals as uncorrelated inter-annual variation. The MS of the residuals was also used or generating randomscatter in the external variables between years.

    The stock model was run for 10 500 (for sprat 40 500) years, under which the  first 500 years were not generating data and were only used to release the dependence on the initially set conditions. The time series of yields and SSB were collected. The runs were repeated for intervals of F to frame the maximum average yields with a step of 0.01. A weighted catchability (as estimated for each species) was applied so that the  F denoted the average for a given range of age-classes. We also present F MSY max and F MSY min which frames the range in which the average yields within 95% of the MSY (WKFRAME-2 2011). The B trigger is set as the lower 2.5 % percentile of the SSBs from the simulation.

  • 129.
    Holmgren, Noél M. A.
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Norrström, Niclas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Aps, R.
    University of Tartu, Estonian Marine Institute, Tallin, Estonia.
    Kuikka, S.
    Fisheries and Environmental Management Group, University of Helsinki, Finland.
    MSY oriented management of the Baltic Sea herring under regime shifts2011In: ICES report of the Baltic Fisheries Assessment working Group (WGBFAS), Copenhagen: ICES , 2011, p. 752-798Chapter in book (Other academic)
    Abstract [en]

    The ecosystem of the baltic sea has undergone dramatic changes, perhaps a regime-shift, during the last four decades. The Baltic Sea Herring SSB has declined to a third and weight-at-age has halved due to plankton prey deficits. The management objective of the herring is currently in the transition to a cautionary maximum sustainable yield (MSY). We modelled the main basin Baltic Sea herring under the currernt regime, and analysed the effect of a ercovery of the cod stock and the food availability as they were in the early 1980s. We recommend a target F MSY of 0.16, but with a recovery of the cod, recommended target F MSY is is 0.10. A simultaneous increase in both cod and food availability is estimated to increase the yield with 40% at the target F MSY is 0.20. We present functions to calculate F MSY and estimate the expected yield depending on the abundance of cod and food-availability. A retrospective application of our functions indicates over-fishing in the 1990s  and early 2000s, and a net loss in yields with a landing value of about E440 Millions.

  • 130.
    Holmgren, Noél M. A.
    et al.
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Norrström, Niclas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Aps, Robert
    University of Tartu, Estonian Marine Institute, Tallin, Estonia.
    Kuikka, Sakari
    Fisheries and Environmental Management Group, Department of Environmental Sciences, University of Helsinki, Finland.
    MSY-orientated management of Baltic Sea herring (Clupea harengus) during different ecosystem regimes2012In: ICES Journal of Marine Science, ISSN 1054-3139, E-ISSN 1095-9289, Vol. 69, no 2, p. 257-266Article in journal (Refereed)
    Abstract [en]

    The Baltic Sea ecosystem has undergone dramatic changes, so-called ecosystem regime shifts, during the past four decades. Baltic Sea herring (Clupea harengus) spawning-stock biomass has declined to a third, and weight-at-age has halved as a result of food shortages and competition with sprat (Sprattus sprattus). The management objective for the herring stock is currently in transition from precautionary to maximum sustainable yield (MSY). The main basin Baltic Sea herring was modelled under the current ecosystem regime and the effect of a recovery of the cod (Gadus morhua) stock and the availability of planktonic food to levels found in the early 1980s analysed. A target of F-MSY = 0.16 for herring, which should decline to F-MSY = 0.10 with recovery of the cod stock, is proposed. An increase in the availability of planktonic food is estimated to more than double the yield at F-MSY = 0.27, overriding the negative effects of cod predation should there be a simultaneous increase in both cod and availability of planktonic food. The estimated net increase in yield is 40% at F-MSY = 0.20. Functions are presented to calculate FMSY and to estimate the expected yield depending on the abundance of cod and food availability. Retrospective application of the functions is indicative of overfishing of herring in the 1990s and early 2000s, and a net loss in yield, with a landing value of some E440 million.

  • 131.
    Holmgren, Noél
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Norrström, Niclas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Aps, Robert
    University of Tartu, Estonia.
    Kuikka, Sakari
    University of Helsinki, Finland.
    A Concept of Bayesian Regulation in Fisheries Management2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, article id e111614Article in journal (Refereed)
    Abstract [en]

    Stochastic variability of biological processes and uncertainty of stock properties compel fisheries managers to look for tools to improve control over the stock. Inspired by animals exploiting hidden prey, we have taken a biomimetic approach combining catch and effort in a concept of Bayesian regulation (BR). The BR provides a real-time Bayesian stock estimate, and can operate without separate stock assessment. We compared the performance of BR with catch-only regulation (CR), alternatively operating with N-target (the stock size giving maximum sustainable yield, MSY) and F-target (the fishing mortality giving MSY) on a stock model of Baltic Sea herring. N-targeted BR gave 3% higher yields than F-targeted BR and CR, and 7% higher yields than N-targeted CR. The BRs reduced coefficient of variance (CV) in fishing mortality compared to CR by 99.6% (from 25.2 to 0.1) when operated with F-target, and by about 80% (from 158.4 to 68.4/70.1 depending on how the prior is set) in stock size when operated with N-target. Even though F-targeted fishery reduced CV in pre-harvest stock size by 19–22%, it increased the dominant period length of population fluctuations from 20 to 60–80 years. In contrast, N-targeted BR made the periodic variation more similar to white noise. We discuss the conditions when BRs can be suitable tools to achieve sustainable yields while minimizing undesirable fluctuations in stock size or fishing effort.

  • 132.
    Holmén, Jonathan
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Jansson, Andreas
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Larsson, Dennis
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    A Kinetic Overview of the Receptors Involved in 1,25-Dihydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 Signaling: A Systems Biology Approach2009In: Critical Reviews in Eukaryotic Gene Expression, ISSN 1045-4403, E-ISSN 2162-6502, Vol. 19, no 3, p. 181-196Article, review/survey (Refereed)
    Abstract [en]

    The vitamin D endocrine system modulates an arsenal of important biological functions in more than 30 different tissues in short- and long-term perspectives. Two membrane receptors and one nuclear receptor are suggested to be involved in the vitamin D signaling system, but the function and physiological relevance of the receptors are debated. The complexity of the vitamin D endocrine system makes it necessary to combine experimental data with in silico simulations to get a holistic view of vitamin D-dependent regulation of tissue and cell physiology. This review focus on binding characteristics for the three putative vitamin D receptors and proposes a future systems biology approach including mathematical modeling that will be helpful together with experimental methods in depicting antitumoral and other biological effects promoted by the vitamin D endocrine system.

  • 133.
    Horning, Aaron M.
    et al.
    University of Texas Health Science Center, San Antonio, USA.
    Awe, Julius Adebayo
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada / Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wang, Chiou-Miin
    University of Texas Health Science Center, San Antonio, USA.
    Liu, Joseph
    University of Texas Health Science Center, San Antonio, USA.
    Lai, Zhao
    University of Texas Health Science Center, San Antonio, USA.
    Wang, Vickie Yao
    University of Texas Health Science Center, San Antonio, USA.
    Jadhav, Rohit R.
    University of Texas Health Science Center, San Antonio, USA.
    Louie, Anna D.
    University of Texas Health Science Center, San Antonio, USA.
    Lin, Chun-Lin
    University of Texas Health Science Center, San Antonio, USA.
    Kroczak, Tad
    University of Manitoba, Winnipeg, Manitoba, Canada.
    Chen, Yidong
    University of Texas Health Science Center, San Antonio, USA.
    Jin, Victor X.
    University of Texas Health Science Center, San Antonio, USA.
    Abboud-Werner, Sherry L.
    University of Texas Health Science Center, San Antonio, USA.
    Leach, Robin J.
    University of Texas Health Science Center, San Antonio, USA.
    Hernandez, Javior
    University of Texas Health Science Center, San Antonio, USA.
    Thompson, Ian M.
    University of Texas Health Science Center, San Antonio, USA.
    Saranchuk, Jeff
    University of Manitoba, Winnipeg, Canada.
    Drachenberg, Darrel
    University of Manitoba, Winnipeg, Canada.
    Chen, Chun-Liang
    University of Texas Health Science Center, San Antonio, USA.
    Mai, Sabine
    University of Manitoba, Winnipeg, Canada.
    Huang, Tim Hui-Ming
    University of Texas Health Science Center, San Antonio, USA.
    DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence2015In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 15, p. 1790-1801Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.

  • 134.
    Hossain, Monayem
    et al.
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Khatun, Most Amena
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Haque, Najmul
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Bari, Azizul
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh / Institute of Biological Sciences, University of Rajshahi, Rajshahi, Bangladesh.
    Alam, Firoz
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kabir, Ahmad Humayan
    Molecular Plant Physiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
    Silicon alleviates arsenic-induced toxicity in wheat through vacuolar sequestration and ROS scavenging2018In: International journal of phytoremediation, ISSN 1522-6514, E-ISSN 1549-7879, Vol. 20, no 8, p. 796-804Article in journal (Refereed)
    Abstract [en]

    Arsenic (As) is a phytotoxic element causing health hazards. This work investigates whether and how silicon (Si) alleviates As toxicity in wheat. The addition of Si under As-stress significantly improved morphophysiological characteristics, total protein, and membrane stability compared to As-stressed plants, suggesting that Si does have critical roles in As detoxification in wheat. Analysis of arsenate reductase activity and phytosiderophore (PS) release reveals their no involvement in the Si-mediated alleviation of As in wheat. Furthermore, Si supplementation in As-stressed plants showed a significant increase of As in roots but not in shoots compared with the plants grown under As stress. Further, gene expression analysis of two chelating molecules, TaPCS1 (phytochelatin synthase) and TaMT1 (metallothionein synthase) showed significant induction due to Si application under As stress compared with As-stressed plants. It is consistent with the physiological observations and suggests that alleviation of As toxicity in rice might be associated with As sequestration in roots leading to reduced As translocation in shoots. Furthermore, increased catalase, peroxidase, and glutathione reductase activities in roots imply the active involvement of reactive oxygen species scavenging for protecting wheat plants from As-induced oxidative injury. The study provides mechanistic evidence on the beneficial effect of Si on As toxicity in wheat plants.

  • 135.
    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
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Spence, Michael
    Department of Animal and Plant Sciences, Sheffield, United Kingdom.
    Holmgren, Noél
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    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, Iceland2017Report (Other academic)
    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.

  • 136.
    Howell, Daniel
    et al.
    Institute of Marine Research, Nordnes, Norway.
    Kempf, Alexander
    Thuenen Institute of Sea Fisheries, Hamburg, Germany.
    Belgrano, Andrea
    Swedish University of Agricultural Sciences, Dept. Aquatic Resources, Lysekil, Sweden.
    Thorpe, Robert
    Centre for Environment, Fisheries and Aquaculture Science, Suffolk, United Kingdom.
    Vinther, Morten
    DTU-Aqua, Charlottenlund, Denmark.
    Bartolino, Valerio
    Swedish University of Agricultural Sciences, Dept. Aquatic Resources, Lysekil, Sweden.
    Pope, John
    NRC (Europe) Ltd.
    Perez Rodriguez, Alfonso
    Wageningen Marine Research.
    Gaichas, Sarah
    NOAA Northeast Fisheries Science Center, Woods Hole, MA, USA.
    Cerviño, Santiago
    Instituto Españo de Oceanografia, Spain.
    Norrström, Niclas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Spence, Michael
    Centre for Environment, Fisheries and Aquaculture Science, Suffolk, United Kingdom.
    Villanueva, Ching
    French Institute of Research for the Exploitation of the sea, Plouzané, France.
    Kulatska, Nataliia
    Swedish University of Agricultural Sciences, Dept. of Aquatic Resources, Lysekil, Sweden.
    Sturludottir, Erla
    Science Institution, University of Iceland, Iceland.
    Trijoulet, Vanessa
    Northeast Fisheries Science Center, Woods Hole, MA, USA.
    Rindorf, Anna
    DTU-Aqua, Charlottenlund, Denmark.
    Andonegi, Eider
    AZTI, Pasaia, Spain.
    Altuna, Miren
    AZTI, Pasaia, Spain.
    Sánchez Maroño, Sonia
    AZTI, Pasaia, Spain.
    Urtizberea, Agurtzane
    AZTI, Pasaia, Spain.
    Interim Report of the Working Group on Multispecies Assessment Methods (WGSAM)2018Report (Other academic)
    Abstract [en]

    The pan-regional Working Group on Multispecies Assessment Methods (WGSAM) met in San Sebastian, Spain, 16–20 October 2017. In this eleventh report of the group, work focused on three of the multi-annual ToRs (B, C, D). 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. A Key Run (ToR B) of the North Sea Stochastic Multispecies Model (SMS) 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 a subset of experts post-meeting. The Key Run is documented in detail in Annex for ToR B, with key outputs summarised in Section 5 and data files made available on the WGSAM webpage and the ICES expert group Github (https://github.com/iceseg/wg_WGSAM). Since the M2 values are used for the assessment of important North Sea stocks, it is recommended to publish the annex also on the official stock annex website. In addition, WGSAM does not recommend updating existing data series of natural mortality by simply adding the latest three new years. The timeseries as a whole shows patterns which are not retained by this procedure. Multispecies model skill assessment (ToR C) and multi-model ensemble methods (ToR D) were emphasized this year. Considerable progress has been made towards advancing both aspects of multispecies modelling. Investigation of skill assessment and ensemble methods and case studies is critical to ensure that outputs of multispecies assessment models are reliable for use in operational assessment and to inform management decisions. Progress was also made on investigations of top predator impacts on managed fish across several regions (ToR F), including the North Sea where new information was included in the SMS key run. Further progress was also made on multispecies and ecosystem level reference points and harvest control rules in mixed fisheries (ToR G).

  • 137.
    Howell, Daniel
    et al.
    Institute of Marine Research, Norway.
    Kempf, Alexander
    Thuenen Institute of Sea Fisheries, Germany.
    Mackinson, Steve
    Centre for Environment, Fisheries and aquaculture science, UK.
    Rindorf, Anna
    DTU Aqua Charlottenlund, Denmark.
    Belgrano, Andrea
    Swedish University of Agricultural Sciences, Sweden.
    Filin, Anatoly
    The Polar Research Institute of Marine Fisheries and Oceanography, Russia.
    Thorpe, Robert
    Centre for Environment, Fisheries and Aquaculture Science, UK.
    Andonegi, Eider
    AZTI-Tecnalia Txatxarramendi Ugartea z/g 48395 Sukarrieta, Spain.
    Tomczak, Maciej
    Stockholm University Baltic Sea Centre, Sweden.
    Lundy, Mathieu
    Agri-food and Biosciences Institute, Belfast, UK.
    Norrström, Nicas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Sand Jacobsen, Nis
    DTU Aqua, Centre for Ocean Life, Denmark.
    Interim Report of the Working Group on Multispecies Assessment Methods (WGSAM): 21-25 October 2013, Stockholm, Sweden2013Report (Other academic)
  • 138.
    Howell, Daniel
    et al.
    Institute of Marine Research, Nordnes, Norway.
    Mackinson, Steve
    CEFAS, United Kingdom.
    Kempf, Alexander
    Thuenen Institute of Sea Fisheries, Hamburg, Germany.
    Rindorf, Anna
    DTU-Aqua, Charlottenlund, Denmark.
    Belgrano, Andrea
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Institute of Marine Research, Lysekil, Sweden / Swedish Institute for the Marine Environment (SIME), Göteborg, Sweden.
    Thorpe, Robert
    Centre for Environment, Fisheries and Aquaculture Science (CEFAS), United Kingdom.
    Vinther, Morten
    DTU-Aqua, Charlottenlund, Denmark.
    Bartolino, Valerio
    Swedish University of Agricultural Sciences, Department of Aquatic Resources, Institute of Marine Research, Lysekil, Sweden.
    Pope, John
    NRC (Europe) Ltd.
    Rodriguez, Alfonso Perez
    Institute of Marine Research, Nordnes, Norway.
    Garcia, Clement
    Centre for Environment, Fisheries and Aquaculture Science (CEFAS), United Kingdom.
    Lehuta, Sigrid
    French Institut of Research for the Exploitation of the Sea (Ifremer), Nantes, France .
    Kaplan, Isaac
    NOAA Northwest Fisheries Science Center, Seattle, USA.
    Gaichas, Sarah
    NOAA Northeast Fisheries Science Center, Woods Hole, USA.
    Kiersten, Curti
    NOAA National Marine Fisheries Service, Northeast Fisheries Science Center, Woods Hole, USA.
    Lucey, Sean
    Dept. of Commerce/NOAA/NMFS Northeast Fisheries Science Center, Woods Hole, USA.
    Gamble, Robert
    NOAA Northeast Fisheries Science Center, Woods Hole, USA.
    Cole, Harriet
    Marine Lab, Marine Scotland Science, Aberdeen, United Kingdom.
    Lindstrom, Ulf
    Instittute of Marine Research, Tromsø, Norway.
    Holmgren, Noel
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Villanueva, Ching
    French Institut of Research for the Exploitation of the Sea (Ifremer), Plouzané, France.
    Poos, Jan Jaap
    IMARES, IJmuiden, The Netherlands.
    Report of the Working Group on Multispecies Assessment Methods (WGSAM), 9–13 November 2015, Woods Hole, USA2016Report (Other academic)
    Abstract [en]

    Three meetings were held between 2013 and 2015 (Stockholm, London and Woods Hole), with progress being made on all the Terms of Reference. WGSAM has been making significant contributions required to enable ICES to develop its capability to give advice on the ecosystem impacts of fishing and climate change. This is a priority area identified in the ICES strategic plan and is consistent with scientific needs to support implementation of the Common Fisheries Policy and Marine Strategy Framework Directive. This final report summarises the key progress made against each ToR. A particularly important area established during this period has been the discussions that have led to guidelines on quality assurance of ecosystem models in-tended for advice giving. WGSAM prepared a specific briefing on this issue and con-tinues to work on issues related to model review processes, model validation and developing methods for generating advice from multi-model ensembles. These are all important areas of work in the evolution toward giving integrated, ecosystem-based advice to ICES clients. We recommend that ICES supports continuation of WGSAM new ToRs and considers more specifically how to support WGSAM in developing advice relevant products.

  • 139.
    Hu, Chun
    et al.
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Song, Gang
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Zhang, Bing
    Xiamen Univ, Coll Med, Dept Basic Med, Xiamen 361005, Peoples R China.
    Liu, Zhongchen
    Xiamen Univ, Coll Med, Zhongshan Affiliated Hosp, Xiamen 361005, Peoples R China .
    Chen, Rong
    Wuhan Inst Technol, Minist Educ, Key Lab Green Chem Proc, Wuhan, Peoples R China and Wuhan Inst Technol, Minist Educ, Sch Chem Engn & Pharm, Wuhan, Peoples R China .
    Zhang, Hong
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Hu, Tianhui
    Xiamen Univ, Coll Med, Canc Res Ctr, Xiamen 361005, Peoples R China .
    Intestinal metabolite compound K of panaxoside inhibits the growth of gastric carcinoma by augmenting apoptosis via Bid-mediated mitochondrial pathway2012In: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 16, no 1, p. 96-106Article in journal (Refereed)
    Abstract [en]

    Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of panaxoside, has been shown to inhibit tumour growth in a variety of tumours. However, the mechanisms involved are largely unknown. We use human gastric carcinoma cell lines BGC823, SGC7901 and human gastric carcinoma xenograft in nude mice as models to study the mechanisms of CK in gastric cancers. We found that CK significantly inhibits the viabilities of BGC823 and SGC7901 cells in dose- and time-dependent manners. CK-induced BGC823 and SGC7901 cells apoptosis and cell cycle arrest in G2 phase by up-regulation of p21 and down-regulation of cdc2 and cyclin B1. Further studies show that CK induces apoptosis in BGC823 and SGC7901 cells mainly through mitochondria-mediated internal pathway, and that CK induces the translocation of nuclear Bid to mitochondria. Finally, we found that CK effectively inhibited the tumour formation of SGC7901 cells in nude mice. Our studies show that CK can inhibit the viabilities and induce apoptosis of human gastric carcinoma cells via Bid-mediated mitochondrial pathway.

  • 140.
    Humayan Kabir, Ahmad
    et al.
    School of Biological Sciences, Flinders University, Australia.
    Mandal, Abul
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Nodularia spumigena and Its Attribute to Bloom Formation in the Baltic Sea2012In: Environmental Research, Engineering and Management, ISSN 1392-1649, E-ISSN 2029-2139, Vol. 1, no 59, p. 5-9Article in journal (Refereed)
    Abstract [en]

    N. spumigena is a dominant cyanobacterial species found in the Baltic Sea. It forms extensive bloom in late summer in the areas of the Baltic Sea with high phosphorus concentrations and moderate salinity. Both environmental and manmade factors are involved in bloom formation. This review also elucidates the physiological and molecular aspects of nitrogen fixation, heterocyst formation and nodularin production in N. spumigena.

  • 141.
    Hurme, Mikko
    et al.
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Early processing in primary visual cortex is necessary for conscious and unconscious vision while late processing is necessary only for conscious vision in neurologically healthy humans2017In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 150, p. 230-238Article in journal (Refereed)
    Abstract [en]

    The neural mechanisms underlying conscious and unconscious visual processes remain controversial. Blindsight patients may process visual stimuli unconsciously despite their VI lesion, promoting anatomical models, which suggest that pathways bypassing the VI support unconscious vision. On the other hand, physiological models argue that the major geniculostriate pathway via VI is involved in both unconscious and conscious vision, but in different time windows and in different types of neural activity. According to physiological models, feedforward activity via VI to higher areas mediates unconscious processes whereas feedback loops of recurrent activity from higher areas back to VI support conscious vision. With transcranial magnetic stimulation (TMS) it is possible to study the causal role of a brain region during specific time points in neurologically healthy participants. In the present study, we measured unconscious processing with redundant target effect, a phenomenon where participants respond faster to two stimuli than one even when one of the stimuli is not consciously perceived. We tested the physiological feedforward-feedback model of vision by suppressing conscious vision by interfering selectively either with early or later VI activity with TMS. Our results show that early VI activity (60 ms) is necessary for both unconscious and conscious vision. During later processing stages (90 ms), VI contributes selectively to conscious vision. These findings support the feedforward-feedback-model of consciousness.

  • 142.
    Hurme, Mikko
    et al.
    Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland / Department of Clinical Neurophysiology, University of Turku and Turku University Hospital, Finland.
    V1 activity during feedforward and early feedback processing is necessary for both conscious and unconscious motion perception2019In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 185, p. 313-321Article in journal (Refereed)
    Abstract [en]

    The study of blindsight has revealed a seminal dissociation between conscious vision and visually guided behavior: some patients who are blind due to V1 lesions seem to be able to employ unconscious visual information in their behavior. The standard assumption is that these findings generalize to the neurologically healthy. We tested whether unconscious processing of motion is possible without the contribution of V1 in neurologically healthy participants by disturbing activity in V1 using transcranial magnetic stimulation (TMS). Unconscious processing was measured with redundant target effect (RTE), a phenomenon where participants respond faster to two stimuli than to one stimulus, when the task is just to respond as fast as possible when one stimulus or two simultaneous stimuli are presented. We measured the RTE caused by a motion stimulus. V1 activity was interfered with different stimulus onset asynchronies (SOA) to test whether TMS delivered in a specific time window suppresses conscious perception (participant reports seeing only one of the two stimuli) but does not affect unconscious processing (RTE). We observed that at each SOA, when TMS suppressed conscious perception of the stimulus, the RTE was also eliminated. However, when visibility of the redundant target was suppressed with a visual mask, we found unconscious processing of motion. This suggests that unconscious processing of motion depends on V1 in neurologically healthy humans. We conclude that the neural mechanisms that enable motion processing in blindsight are modulated by neuroplastic changes in connectivity between subcortical areas and the visual cortex after the V1 lesion. Neurologically healthy observers cannot process motion unconsciously without functioning of V1. 

  • 143.
    Håkansson, Nina
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Network analysis and optimization of animal transports2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is about animal transports and their effect on animal welfare. Transports are needed in today’s system of livestock farming. Long transports are stressful for animals and infectious diseases can spread via animal transports. With optimization methods transport times can be minimized, but there is a trade-off between short distances for the animals and short distances for the trucks. The risk of disease spread in the transport system and disease occurrence at farms can be studied with models and network analysis.

    The animal transport data and the quality of the data in the Swedish national database of cattle and pig transports are investigated in the thesis. The data is analyzed regarding number of transports, number of farms, seasonality, geographical properties, transport distances, network measures of individual farms and network measures of the system. The data can be used as input parameters in epidemic models.

    Cattle purchase reports are double reported and we found that there are incorrect and missing reports in the database. The quality is improving over the years i.e. 5% of cattle purchase reports were not correctly double reported in 2006, 3% in 2007 and 1% in 2008. In the reports of births and deaths of cattle we detected date preferences; more cattle births and deaths are reported on the 1st, 10th and 20th each month. This is because when we humans don’t remember the exact number we tend to pick nice numbers (like 1, 10 and 20). This implies that the correct date is not always reported.

    Network analysis and network measures are suggested as tools to estimate risk for disease spread in transport systems and risk of disease introduction to individual holdings. Network generation algorithms can be used together with epidemic models to test the ability of network measures to predict disease risks. I have developed, and improved, a network generation algorithm that generates a large variety of structures.

    In my thesis I also suggest a method, the good choice heuristic, for generating non-optimal routes. Today coordination of animal transports is neither optimal nor random. In epidemic simulations we need to model routes as close to the actual driven routes as possible and the good choice heuristic can model that. The heuristic is tuned by two parameters and creates coordination of routes from completely random to almost as good as the Clarke and Wright heuristic. I also used the method to make the rough estimate that transport distances for cattle can be reduced by 2-24% with route-coordination optimization of transports-to-slaughter.

    Different optimization methods can be used to minimize the transport times for animal-transports in Sweden. For transports-to-slaughter the strategic planning of “which animals to send where” is the first step to optimize. I investigated data from 2008 and found that with strategic planning, given the slaughterhouse capacity, transport distances can be decreased by about 25% for pigs and 40% for cattle. The slaughterhouse capacity and placement are limiting the possibility to minimize transport times for the animals. The transport distances could be decreased by 60% if all animals were sent to the closest slaughterhouse 2008. Small-scale and mobile slaughterhouses have small effect on total transport work (total transport distance for all the animals) but are important for the transport distances of the animals that travel the longest.

     

     

  • 144.
    Håkansson, Nina
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Flisberg, P.
    Forestry Research Institute of Sweden, Uppsala, Sweden.
    Algers, B.
    Swedish University of Agricultural Sciences, Skara, Sweden.
    Jonsson, Annie
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Rönnqvist, M.
    Forestry Research Institute of Sweden, Uppsala, Sweden / University Laval, Quebec City, Canada.
    Wennergren, U.
    Linköping University, Department of Physics, Chemistry and Biology, Linköping, Sweden.
    Improvement of animal welfare by strategic analysis and logistic optimisation of animal slaughter transportation2016In: Animal Welfare, ISSN 0962-7286, Vol. 25, no 2, p. 255-263Article in journal (Refereed)
    Abstract [en]

    The transportation of animals to slaughterhouses is a major welfare concern. The number of slaughterhouses has decreased over time in Europe due to centralisation. This is expected to increase transport time for animals and as a consequence negatively affect animal welfare. We propose an optimisation model based on a facility location model to perform strategic analysis to improve transportation logistics. The model is tested on the Swedish slaughter transport system. We show that, by strategic planning and redirection of transports while keeping the slaughterhouse capacities as of the originaldata, the potential exists to reduce transport distance by 25% for pigs and 40% for cattle. Furthermore, we demonstrated that approximately 50% of Swedish slaughterhouses can be shut down with a minimal effect on total transport distances. This implies that in terms of the overall welfare picture, the decision of which animals to send where plays a for more significant role than the number of slaughterhouses. In addition, by changing relative weights on distances in the optimisation function the amount of individualtransports with longjourney times can be decreased. We also show results from altered slaughterhouse capacity and geographical location of slaughterhouses. This is the first time an entire country has been analysed in great detail with respect to the location, capacity and number of slaughterhouses. The focus is mainly on the analysis of unique and detailed information of actual animal transports in Sweden and a demonstration of the potential impact redirection of the transports and/ or altering of slaughterhouses can have on animal welfare.

  • 145.
    Håkansson, Nina
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Jonsson, Annie
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lennartsson, Jenny
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Lindström, T.
    Linköping University.
    Wennergren, U.
    Linköping University.
    Generating Structure Specific Networks2010In: Advances in Complex Systems, ISSN 0219-5259, Vol. 13, no 2, p. 239-250Article in journal (Refereed)
    Abstract [en]

    Theoretical exploration of network structure significance requires a range of different networks for comparison. Here, we present a new method to construct networks in a spatial setting that uses spectral methods in combination with a probability distribu-tion function. Nearly all previous algorithms for network construction have assumed randomized distribution of links or a distribution dependent on the degree of the nodes.We relax those assumptions. Our algorithm is capable of creating spectral networks along a gradient from random to highly clustered or diverse networks. Number of nodes and link density are specified from start and the structure is tuned by three parameters (γ, σ, κ). The structure is measured by fragmentation, degree assortativity, clusteringand group betweenness of the networks. The parameter γ regulates the aggregation in the spatial node pattern and σ and κ regulates the probability of link forming.

  • 146. Ingvarsson, Per
    et al.
    Rydgård, Mats
    Jonsson, Annie
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Föryngring hos stormusslor i olika vattensystem i Västra Götalands län 20082009Report (Other academic)
    Abstract [sv]

    I elva vattensystem har 19 provytor analyserats på förekomst av juvenila och adulta musslor. Juvenila musslor saknas helt eller delvis i flera provytor.

  • 147.
    Intaite, Monika
    et al.
    Visual Neuroscience Laboratory, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
    Koivisto, Mika
    Centre for Cognitive Neuroscience, University of Turku, Turku, Finland / Department of Psychology, University of Turku, Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Humanities and Informatics. University of Skövde, The Systems Biology Research Centre. Centre for Cognitive Neuroscience, University of Turku, Turku, Finland / Department of Psychology, University of Turku, Turku, Finland.
    Perceptual reversals of Necker stimuli during intermittent presentation with limited attentional resources2013In: Psychophysiology, ISSN 0048-5772, E-ISSN 1469-8986, Vol. 50, no 1, p. 82-96Article in journal (Refereed)
    Abstract [en]

    During prolonged viewing of ambiguous stimuli, such as Necker cubes, sudden perceptual reversals occur from one perceptual interpretation to another. The role of attention in such reversals is not clear. We tested whether perceptual reversals depend on attentional resources by manipulating perceptual load and recording event-related potentials (ERPs) during intermittent presentation of Necker stimuli. The results did not reveal any influence for perceptual load on the frequency of reversals. The ERPs showed that perceptual load influenced electrophysiological activity over parieto-central areas in the P1 time window (110–140 ms), but load did not modify the early enhancements of positivity (30–140 ms), which correlated with perceptual reversals at occipito-temporal sites. We conclude that disambiguation of ambiguous figures is based on early mechanisms that can work efficiently with only a minimal amount of attentional resources.

  • 148.
    Islam, Khairul
    et al.
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Haque, Abedul
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Karim, Rezaul
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh / Islamic Univ, Dept Appl Nutr & Food Technol, Kushtia 7003, Bangladesh / UMP, FIST, Gambang 26300, Pahang, Malaysia .
    Fajol, Abul
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Hossain, Ekhtear
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Salam, Kazi Abdus
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Ali, Nurshad
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Saud, Zahangir Alam
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Rahman, Matiar
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Rahman, Mashiur
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Sultana, Papia
    Rajshahi Univ, Dept Stat, Rajshahi 6205, Bangladesh .
    Hossain, Mostaque
    Bangladesh Inst Res & Rehabil Diabet Endocrine &, Dept Med, Dhaka, Bangladesh .
    Akhand, Anwarul Azim
    Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh .
    Mandal, Abul
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Miyataka, Hideki
    Tokushima Bunri Univ, Lab Mol Nutr & Toxicol, Fac Pharmaceut Sci, Tokushima 7708514, Japan.
    Himeno, Seiichiro
    Tokushima Bunri Univ, Lab Mol Nutr & Toxicol, Fac Pharmaceut Sci, Tokushima 7708514, Japan.
    Hossain, Khaled
    Rajshahi Univ, Dept Biochem & Mol Biol, Rajshahi 6205, Bangladesh .
    Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh2011In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 10, p. 64-Article in journal (Refereed)
    Abstract [en]

    Background: Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods: A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. Results: Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. Conclusions: The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.

  • 149.
    Islam, Md Shofikul
    et al.
    University of Rajshahi, Bangladesh / Islamic University, Kushtia-7003, Bangladesh.
    Mohanto, Nayan Chandra
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Karim, Md Rezaul
    Islamic University, Kushtia-7003, Bangladesh.
    Aktar, Sharmin
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Hoque, Md Mominul
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Rahman, Atiqur
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Jahan, Momotaj
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Khatun, Rabeya
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Aziz, Abdul
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Abdus Salam, Kazi
    University of Rajshahi, Rajshahi-6205, Bangladesh / National institutes of Health, Bethesda, USA.
    Saud, Zahangir Alam
    University of Rajshahi, Rajshahi-6205, Bangladesh.
    Hossain, Mostaque
    Kaliganj Upazila Health Complex, Gazipur, Dhaka, Bangladesh.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Haque, Azizul
    Medical University of South Carolina, Charleston, SC, USA.
    Miyataka, Hideki
    Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
    Himeno, Seiichiro
    Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
    Hossain, Khaled
    Department of Biochemistry and Molecular Biology, University of Rajshahi, Bangladesh.
    Elevated concentrations of serum matrix metalloproteinase-2 and -9 and their associations with circulating markers of cardiovascular diseases in chronic arsenic-exposed individuals2015In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 14, no 1, article id 92Article in journal (Refereed)
    Abstract [en]

    Background: Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and −9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs.

    Methods: A total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits.

    Results: Serum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (rs = 0.208, p < 0.001 for MMP-2; rs = 0.163, p <0.01 for MMP-9), hair (rs= 0.163, p < 0.01 for MMP-2; rs = 0.173, p < 0.01 for MMP-9) and nail (rs= 0.160, p < 0.01 for MMP-2; rs = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 μg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs.

    Conclusions: This study showed the significant positive associations and dose–response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.

  • 150.
    Jacob, Ute
    et al.
    University of Hamburg, Inst Hydrobiol & Fisheries Sci, Hamburg, Germany.
    Thierry, Aaron
    University of Sheffield, Dept Anim & Plant Sci, Western Bank, Sheffield S10 2TN, S Yorkshire, England / Microsoft Res, Cambridge, England.
    Brose, Ulrich
    Georg-August University Göttingen JF Blumenbach Inst Zool & Anthropol, Syst Conservat Biol Grp, Göttingen, Germany.
    Arntz, Wofe E.
    Alfred Wegener Inst Polar & Marine Res, Bremerhaven, Germany.
    Berg, Sofia
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Brey, Thomas
    Alfred Wegener Institute for Polar and Marine Research.
    Fetzer, Ingo
    UFZ Helmholtz Ctr Environm Res, Dept Environm Microbiol, Leipzig, Germany.
    Jonsson, Tomas
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Mintenbeck, Katja
    Alfred Wegener Inst Polar & Marine Res, Bremerhaven, Germany.
    Möllmann, Christian
    Univ Hamburg, Inst Hydrobiol & Fisheries Sci, Hamburg, Germany.
    Petchey, Owen
    Univ Zurich, Inst Evolutionary Biol & Environm Studies, Zurich, Switzerland.
    Riede, Jens O.
    Univ Gottingen, JF Blumenbach Inst Zool & Anthropol, Syst Conservat Biol Grp, Gottingen, Germany.
    Dunne, Jennifer A.
    Santa Fe Inst, Santa Fe, NM 87501 USA / Pacific Ecoinformat & Computat Ecol Lab, Berkeley, CA USA.
    The Role of Body Size in Complex Food Webs: A Cold Case2011In: Advances in Ecological Research, ISSN 0065-2504, E-ISSN 2163-582X, Vol. 45, p. 181-223Article in journal (Refereed)
    Abstract [en]

    Human-induced habitat destruction, overexploitation, introduction of alien species and climate change are causing species to go extinct at unprecedented rates, from local to global scales. There are growing concerns that these kinds of disturbances alter important functions of ecosystems. Our current understanding is that key parameters of a community (e.g. its functional diversity, species composition, and presence/absence of vulnerable species) reflect an ecological network’s ability to resist or rebound from change in response to pressures and disturbances, such as species loss. If the food web structure is relatively simple, we can analyse the roles of different species interactions in determining how environmental impacts translate into species loss. However, when ecosystems harbour species-rich communities, as is the case in most natural systems, then the complex network of ecological interactions makes it a far more challenging task to perceive how species’ functional roles influence the consequences of species loss. One approach to deal with such complexity is to focus on the functional traits of species in order to identify their respective roles: for instance, large species seem to be more susceptible to extinction than smaller species. Here, we introduce and analyse the marine food web from the high Antarctic Weddell Sea Shelf to illustrate the role of species traits in relation to network robustness of this complex food web. Our approach was threefold: firstly, we applied a new classification system to all species, grouping them by traits other than body size; secondly, we tested the relationship between body size and food web parameters within and across these groups and finally, we calculated food web robustness. We addressed questions regarding (i) patterns of species functional/trophic roles, (ii) relationships between species functional roles and body size and (iii) the role of species body size in terms of network robustness. Our results show that when analyzing relationships between trophic structure, body size and network structure, the diversity of predatory species types needs to be considered in future studies.

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