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  • 1751.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Interactions between the brain and the immune system in pain and inflammation2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Reciprocal interactions between the nervous and immune systems have gained a lot of attention in the last two decades, especially after demonstrating that cytokine immunotherapies can induce depression and after describing the inflammatory reflex. A lot of effort has been dedicated to understanding how the signals from the immune system reach the brain and vice versa, and on their role in health and disease. However, it is not well-known which of the brain circuits, receptors and signalling molecules give rise to behavioural and affective changes induced by inflammation, such as reduced food intake and induction of negative mood. Moreover, although it is well established that early life stress leads to an increased risk of developing inflammatory diseases in adulthood, the acute effects of stress on the inflammatory response in childhood are not well described. Using mouse models of systemic and local inflammation, I studied (1) how inflammatory pain elicits negative affect, (2) if CGRPα is necessary for parabrachial-amygdaloid pathway-mediated behaviours associated with pain and inflammation, and finally, (3) what are the effects of stress on the inflammatory process during early life. The results indicate that (1) the negative affect of inflammatory pain is triggered by inhibition of serotonergic neurons of the dorsal raphe nucleus, as a result of prostaglandin E2 binding to EP3 receptors; (2) CGRPα is dispensable for most pain- and inflammation-related protective behaviours; (3) acute stress potentiates the pro-inflammatory cytokine expression after an inflammatory challenge in mouse pups. The phenomena studied here can contribute to understanding how immune system activation induces changes in mood and behaviour common for inflammation and depression.

    List of papers
    1. Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain
    Open this publication in new window or tab >>Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain
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    2017 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 127, no 4, p. 1370-1374Article in journal (Refereed) Published
    Abstract [en]

    Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E-2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E-2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalininduced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a kappa opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.

    Place, publisher, year, edition, pages
    AMER SOC CLINICAL INVESTIGATION INC, 2017
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-136568 (URN)10.1172/JCI90678 (DOI)000398183300026 ()28287401 (PubMedID)
    Note

    Funding Agencies|European Research Council; Swedish Medical Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain Foundation; County Council of Ostergotland; National Institute of Neurological Disorders and Stroke (NINDS)

    Available from: 2017-04-24 Created: 2017-04-24 Last updated: 2019-04-08
    2. Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
    Open this publication in new window or tab >>Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
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    2019 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 77, p. 141-149Article in journal (Refereed) Published
    Abstract [en]

    Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8–9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated.

    Place, publisher, year, edition, pages
    Elsevier, 2019
    Keywords
    Lipopolysaccharide, Hypothalamus, Cytokines, Inflammation, Maternal separation, Corticosterone
    National Category
    Pharmacology and Toxicology Developmental Biology Medical Biotechnology Immunology
    Identifiers
    urn:nbn:se:liu:diva-154886 (URN)10.1016/j.bbi.2018.12.016 (DOI)000461412600016 ()30590109 (PubMedID)2-s2.0-85059128986 (Scopus ID)
    Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2020-04-20Bibliographically approved
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    Interactions between the brain and the immune system in pain and inflammation
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  • 1752.
    Zajdel, Joanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Zager, Adriano
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Shionoya, Kiseko
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation2019In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 77, p. 141-149Article in journal (Refereed)
    Abstract [en]

    Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8–9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated.

  • 1753.
    Zajitschek, Felix
    et al.
    Monash Univ, Australia; Uppsala Univ, Sweden.
    Georgolopoulos, Grigorios
    Uppsala Univ, Sweden.
    Vourlou, Anna
    Uppsala Univ, Sweden.
    Ericsson, Maja
    Uppsala Univ, Sweden.
    Zajitschek, Susanne R. K.
    Monash Univ, Australia; CSIC, Spain; Uppsala Univ, Sweden.
    Friberg, Urban
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Uppsala Univ, Sweden.
    Maklakov, Alexei A.
    Uppsala Univ, Sweden; Univ East Anglia, England.
    Evolution Under Dietary Restriction Decouples Survival From Fecundity in Drosophila melanogaster Females2019In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 74, no 10, p. 1542-1548Article in journal (Refereed)
    Abstract [en]

    One of the key tenets of life-history theory is that reproduction and survival are linked and that they trade-off with each other. When dietary resources are limited, reduced reproduction with a concomitant increase in survival is commonly observed. It is often hypothesized that this dietary restriction effect results from strategically reduced investment in reproduction in favor of somatic maintenance to survive starvation periods until resources become plentiful again. We used experimental evolution to test this "waiting-for-the-good-times" hypothesis, which predicts that selection under sustained dietary restriction will favor increased investment in reproduction at the cost of survival because "good-times" never come. We assayed fecundity and survival of female Drosophila melanogaster fruit flies that had evolved for 50 generations on three different diets varying in protein content-low (classic dietary restriction diet), standard, and high-in a full-factorial design. High-diet females evolved overall increased fecundity but showed reduced survival on low and standard diets. Low-diet females evolved reduced survival on low diet without corresponding increase in reproduction. In general, there was little correspondence between the evolution of survival and fecundity across all dietary regimes. Our results contradict the hypothesis that resource reallocation between fecundity and somatic maintenance underpins life span extension under dietary restriction.

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  • 1754.
    Zajitschek, Felix
    et al.
    Monash University, Australia; Uppsala University, Sweden.
    Zajitschek, Susanne R. K.
    Uppsala University, Sweden; Spanish Research Council CSIC, Spain.
    Canton, Cindy
    Uppsala University, Sweden.
    Georgolopoulos, Grigorios
    Uppsala University, Sweden.
    Friberg, Urban
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Uppsala University, Sweden.
    Maklakov, Alexei A.
    Uppsala University, Sweden.
    Evolution under dietary restriction increases male reproductive performance without survival cost2016In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 283, no 1825, p. 20152726-Article in journal (Refereed)
    Abstract [en]

    Dietary restriction (DR), a reduction in nutrient intake without malnutrition, is the most reproducible way to extend lifespan in a wide range of organisms across the tree of life, yet the evolutionary underpinnings of the DR effect on lifespan are still widely debated. The leading theory suggests that this effect is adaptive and results from reallocation of resources from reproduction to somatic maintenance, in order to survive periods of famine in nature. However, such response would cease to be adaptive when DR is chronic and animals are selected to allocate more resources to reproduction. Nevertheless, chronic DR can also increase the strength of selection resulting in the evolution of more robust genotypes. We evolved Drosophila melanogaster fruit flies on DR, standard and high adult diets in replicate populations with overlapping generations. After approximately 25 generations of experimental evolution, male DR flies had higher fitness than males from standard and high populations. Strikingly, this increase in reproductive success did not come at a cost to survival. Our results suggest that sustained DR selects for more robust male genotypes that are overall better in converting resources into energy, which they allocate mostly to reproduction.

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  • 1755.
    Zajitschek, Felix
    et al.
    Department of Animal Ecology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Zajitschek, Susanne R. K.
    Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Friberg, Urban
    Department of Evolutionary Biology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Maklakov, Alexei A.
    Department of Animal Ecology, Ageing Research Group, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies2013In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 35, no 4, p. 1193-1204Article in journal (Refereed)
    Abstract [en]

    For the evolution of life histories, the trade-off between survival and reproduction is fundamental. Because sexes optimize fitness in different ways, this trade-off is expected to be resolved differently by males and females. Consequently, the sexes are predicted to respond differently to changes in resource availability. In fruit flies, research on dietary restriction has focused largely on females maintained in the absence of males, thereby neglecting sexual interactions that affect reproductive behavior of both sexes under more natural conditions. Here, we tested for the interactive effects of diet (40, 60, 100, and 300 % of standard yeast concentrations) and social environment (separate-sex vs. mixed-sex groups) on male and female Drosophila melanogaster life histories. Additionally, we evaluated the essential amino acid methionine as an agent that can uncouple the survival-reproduction trade-off. We show sex differences in the effect of social environment on survival patterns, but not on reproductive fitness. In females, yeast had a positive effect on reproduction and a negative effect on survival. In males, yeast had a negative effect on reproduction and the effect on survival depended on the social environment. Methionine reduced survival, but had no effect on reproduction. Our findings highlight the need to include both sexes and to vary social environments in research programs aimed at lifespan extension and call for further evaluation of the fecundity-restoring effect of methionine.

  • 1756.
    Zallar, L J
    et al.
    Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA; Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Tunstall, B J
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Richie, C T
    Genetic Engineering and Viral Vector Core, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Zhang, Y J
    Genetic Engineering and Viral Vector Core, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, Rockville, MD, USA.
    You, Z B
    Neuropsychopharmacology Section, Molecular Targets and Medications Discover Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Gardner, E L
    Neuropsychopharmacology Section, Molecular Targets and Medications Discover Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Psykiatriska kliniken inkl beroendekliniken.
    Pickel, J
    Transgenic Core Facility, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.
    Koob, G F
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Vendruscolo, L F
    Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
    Harvey, B K
    Molecular Mechanisms of Cellular Stress and Inflammation Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA.
    Leggio, L-
    Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA. lorenzo.leggio@nih.gov; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
    Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9 knockout wistar rat model2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 2, p. 344-354Article in journal (Refereed)
    Abstract [en]

    Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing.

  • 1757.
    Zeng, Fan
    et al.
    Univ Innsbruck, Austria.
    Wunderer, Julia
    Univ Innsbruck, Austria.
    Salvenmoser, Willi
    Univ Innsbruck, Austria.
    Ederth, Thomas
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Rothbaecher, Ute
    Univ Innsbruck, Austria.
    Identifying adhesive components in a model tunicate2019In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 374, no 1784, article id 20190197Article in journal (Refereed)
    Abstract [en]

    Tunicates populate a great variety of marine underwater substrates worldwide and represent a significant concern in marine shipping and aquaculture. Adhesives are secreted from the anterior papillae of their swimming larvae, which attach and metamorphose into permanently adhering, filter-feeding adults. We recently described the cellular composition of the sensory adhesive organ of the model tunicate Ciona intestinalis in great detail. Notably, the adhesive secretions of collocytes accumulate at the tip of the organ and contain glycoproteins. Here, we further explore the components of adhesive secretions and have screened for additional specificities that may influence adhesion or cohesion of the Ciona glue, including other carbohydrate moieties, catechols and substrate properties. We found a distinct set of sugar residues in the glue recognized by specific lectins with little overlap to other known marine adhesives. Surprisingly, we also detect catechol residues that likely originate from an adjacent cellular reservoir, the test cells. Furthermore, we provide information on substrate preferences where hydrophobicity outperforms charge in the attachment. Finally, we can influence the settlement process by the addition of hydrophilic heparin. The further analysis of tunicate adhesive strategies should provide a valuable knowledge source in designing physiological adhesives or green antifoulants. This article is part of the theme issue Transdisciplinary approaches to the study of adhesion and adhesives in biological systems.

  • 1758.
    Zhang, Bin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Jansson, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Chen, P-P
    Chinese Acad Sci, Peoples R China.
    Wang, X-J
    Chinese Acad Sci, Peoples R China.
    Chen, Weimin
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Buyanova, Irina
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Effects of Bi incorporation on recombination processes in wurtzite GaBiAs nanowires2020In: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 31, no 22, article id 225706Article in journal (Refereed)
    Abstract [en]

    The effects of Bi incorporation on the recombination process in wurtzite (WZ) GaBiAs nanowires are studied by employing micro-photoluminescence (mu-PL) and time-resolved PL spectroscopies. It is shown that at low temperatures (T amp;lt; 75 K) Bi-induced localization effects cause trapping of excitons within band-tail states, which prolongs their lifetime and suppresses surface nonradiative recombination (SNR). With increasing temperature, the trapped excitons become delocalized and their lifetime rapidly shortens due to facilitated SNR. Furthermore, Bi incorporation in the GaBiAs NW is found to have a minor influence on the surface states responsible for SNR.

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  • 1759.
    Zhang, Wenjun
    et al.
    Chinese Academic Science, Peoples R China .
    Wu, Yulei
    Chinese Academic Science, Peoples R China .
    Bao, Qinye
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, The Institute of Technology.
    Gao, Feng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Fang, Junfeng
    Chinese Academic Science, Peoples R China .
    Morphological Control for Highly Efficient Inverted Polymer Solar Cells Via the Backbone Design of Cathode Interlayer Materials2014In: ADVANCED ENERGY MATERIALS, ISSN 1614-6832, Vol. 4, no 12, p. 1400359-Article in journal (Refereed)
    Abstract [en]

    Two alcohol-soluble organic molecules are synthesized and introduced into inverted organic solar cells as the cathode interlayer. A power conversion efficiency as high as 9.22% is obtained by using the more hydrophobic molecule FTBTF-N as the cathode interlayer. Morphological studies suggest that design of the backbone can help to enhance short-circuit current density and fill factor.

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  • 1760.
    Zhang, Xiaonan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    De Milito, Angelo
    Department of Oncology-Pathology, Karolinska Institute, SE-171 76 Stockholm, Sweden.
    Demiroglu-Zergeroglu, Asuman
    Department of Molecular Biology and Genetics, Gebze Technical University, 41400, Gebze, Kocaeli, Turkey.
    Gullbo, Joachim
    Department of Immunology, Genetics and Pathology, Section of Oncology, Uppsala University, Uppsala, Sweden.
    D’Arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Eradicating Quiescent Tumor Cells by Targeting Mitochondrial Bioenergetics2016In: Trends in Cancer, ISSN 2405-8033, Vol. 2, no 11, p. 7p. 657-663Article, review/survey (Refereed)
    Abstract [en]

    Solid tumors contain slowly proliferating cells that show limited sensitivity to conventional cell cycle-active chemotherapeutic drugs. Tumor cells that are not exposed to therapeutically relevant drug concentrations and/or are insensitive to drugs survive treatment and repopulate tumors between treatment cycles. Cancer cells residing in hypoxic and nutritionally compromised environments are expected to have limited metabolic plasticity and to be susceptible to the manipulation of energy supply pathways. Drug screening campaigns using glucose-depleted tumor cells and 3D tumor cell cultures have resulted in the identification of inhibitors of mitochondrial energy production.

  • 1761.
    Zhang, Xiaonan
    et al.
    Karolinska Institute, Sweden.
    Mofers, Arjan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Hydbring, Per
    Karolinska Institute, Sweden.
    Hagg Olofsson, Maria
    Karolinska Institute, Sweden.
    Guo, Jing
    Karolinska Institute, Sweden; Duke NUS National University of Singapore Medical Sch, Singapore.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    MYC is downregulated by a mitochondrial checkpoint mechanism2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 52, p. 90225-90237Article in journal (Refereed)
    Abstract [en]

    The MYC proto-oncogene serves as a rheostat coupling mitogenic signaling with the activation of genes regulating growth, metabolism and mitochondrial biogenesis. Here we describe a novel link between mitochondria and MYC levels. Perturbation of mitochondrial function using a number of conventional and novel inhibitors resulted in the decreased expression of MYC mRNA. This decrease in MYC mRNA occurred concomitantly with an increase in the levels of tumor-suppressive miRNAs such as members of the let-7 family and miR-34a-5p. Knockdown of let-7 family or miR-34a-5p could partially restore MYC levels following mitochondria damage. We also identified let-7-dependent downregulation of the MYC mRNA chaperone, CRD-BP (coding region determinant-binding protein) as an additional control following mitochondria damage. Our data demonstrates the existence of a homeostasis mechanism whereby mitochondrial function controls MYC expression.

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  • 1762.
    Zhang, Xiaonan
    et al.
    Karolinska Inst, Sweden.
    Selvaraj, Karthik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Saei, Amir Ata
    Karolinska Inst, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Zubarev, Roman A.
    Karolinska Inst, Sweden.
    Arner, Elias S. J.
    Karolinska Inst, Sweden.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Repurposing of auranofin: Thioredoxin reductase remains a primary target of the drug2019In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 162, p. 46-54Article in journal (Refereed)
    Abstract [en]

    Auranofin is a gold (1)-containing compound used for the treatment of rheumatic arthritis. Auranofin has anticancer activity in animal models and is approved for clinical trials for lung and ovarian carcinomas. Both the cytosolic and mitochondrial forms of the selenoprotein thioredoxin reductase (TrxR) are well documented targets of auranofin. Auranofin was recently reported to also inhibit proteasome activity at the level of the proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14. We here set out to re-examine the molecular mechanism underlying auranofin cytotoxicity towards cultured cancer cells. The effects of auranofin on the proteasome were examined in cells and in vitro, effects on DUB activity were assessed using different substrates. The cellular response to auranofin was compared to that of the 20S proteasome inhibitor bortezomib and the 19S DUB inhibitor b-AP15 using proteomics. Auranofin was found to inhibit mitochondrial activity and to an induce oxidative stress response at IC50 doses. At 2-3-fold higher doses, auranofin inhibits proteasome processing in cells. At such supra-pharmacological concentrations USP14 activity was inhibited. Analysis of protein expression profiles in drug-exposed tumor cells showed that auranofin induces a response distinct from that of the 20S proteasome inhibitor bortezomib and the DUB inhibitor b-AP15, both of which induced similar responses. Our results support the notion that the primary mechanism of action of auranofin is TrxR inhibition and suggest that proteasome DUB inhibition is an off-target effect. Whether proteasome inhibition will contribute to the antineoplastic effect of auranofin in treated patients is unclear but remains a possibility. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

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  • 1763.
    Zhang, Xueli
    et al.
    Orebro Univ, Sweden; Soochow Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Shen, Bairong
    Soochow Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Novel MicroRNA Biomarkers for Colorectal Cancer Early Diagnosis and 5-Fluorouracil Chemotherapy Resistance but Not Prognosis: A Study from Databases to AI-Assisted Verifications2020In: Cancers, ISSN 2072-6694, CANCERS, Vol. 12, no 2, article id 341Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.

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  • 1764.
    Zhao, Jin J.
    et al.
    Uppsala University, Sweden.
    Halvardson, Jonatan
    Uppsala University, Sweden.
    Zander, Cecilia S.
    Uppsala University, Sweden.
    Zaghlool, Ammar
    Uppsala University, Sweden.
    Georgii-Hemming, Patrik
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Mansson, Else
    Örebro University Hospital, Sweden.
    Brandberg, Göran
    Pediat Clin, Falun, Sweden.
    Savmarker, Helena E.
    Gävle Central Hospital, Sweden.
    Frykholm, Carina
    Uppsala University, Sweden.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Thuresson, Ann-Charlotte
    Uppsala University, Sweden.
    Feuk, Lars
    Uppsala University, Sweden.
    Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability2018In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 177, no 1, p. 10-20Article in journal (Refereed)
    Abstract [en]

    Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.

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  • 1765.
    Zhen, Hongyu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology. State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, China.
    Hou, Qiong
    S China Normal University, Peoples R China S China University of Technology, Peoples R China .
    Li, Kan
    Zhejiang University, Peoples R China .
    Ma, Zaifei
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Fabiano, Simone
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Gao, Feng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Zhang, Fengling
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Solution-processed bulk-heterojunction organic solar cells employing Ir complexes as electron donors2014In: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 2, no 31, p. 12390-12396Article in journal (Refereed)
    Abstract [en]

    To explore enhancing photocurrent in organic solar cells (OSCs) via harvesting triplet excitons, two novel bicycloiridium complexes (R-1 and R-2) are designed and synthesized. Conventional bulk-heterojunction triplet OSCs are solution processed using R-1 or R-2 as sole electron donors and phenyl-C-71-butyric acid methyl ester (PC71BM) as the electron acceptor. A decent short circuit current (J(sc)) of 6.5 mA cm(-2) is achieved though the overlap between the absorption spectrum (with similar to 550 nm absorption onset) of R-2 and the solar flux is relatively small. With an open circuit voltage of 0.74 V and a fill factor of 0.42, an encouraging power conversion efficiency of 2.0% is achieved in the OSCs based on R-2 and PC71BM without any processing additives and post-treatments. Our preliminary result demonstrates the possibility of utilizing Ir complexes as sole electron donors in OSCs, which extends available soluble small molecules for OSCs.

  • 1766.
    Zhybak, Mikael T
    et al.
    Institute of Molecular Biology and Genetics, NAS of Ukraine, Ukraine.
    Fayura, L.Y.
    Institute of Cell Biology, NAS of Ukraine, Ukraine.
    Boretsky, Yu R
    Institute of Cell Biology, NAS of Ukraine, Ukraine.
    Dempsey, Eithne
    Centre for Research in Electroanalytical Technologies, Ireland.
    Gonchar, M.V.
    Institute of Cell Biology, NAS of Ukraine, Ukraine.
    Sibirny, A.A.
    Institute of Cell Biology, NAS of Ukraine, Ukraine.
    Turner, Anthony
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Korpan, Yaroslav
    Institute of Molecular Biology and Genetics, NAS of Ukraine, Ukraine.
    Novel L-arginine amperometric assay based on recombinant arginine deiminase and Nafion/PANi composite2016In: Biosensors 2016 – The World Congress on Biosensors, Elsevier, 2016Conference paper (Other academic)
  • 1767. Order onlineBuy this publication >>
    Zidar, Josefina
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    The relationship between personality and cognition in the fowl, Gallus gallus2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    To cope with a changing environment, animals have traditionally been considered to behave adaptively to each situation faced. Yet, individual behavioural responses can both differ widely within populations, and show between-individual consistency (i.e. describing variation in animal personality). In this thesis, I focus on individual differences in animal personality and cognition (i.e. how animals perceive, process, store and act on environmental stimuli), and explore the possibility that they are interlinked. I use domestic- and red junglefowl (Gallus gallus ssp.), a species that is cognitively, behaviourally and socially complex, to explore these aspects of behaviour, through a series of studies.

    Animal personality and coping styles are frequently used terms to describe within- and between-individual differences in behaviour, which are consistent over time and across various situations. The terms are often used as synonyms, even though they differ in some respects. In paper I, I show that animal personality and coping styles can be measured in red junglefowl, and that behavioural flexibility might be an important aspect for both. Further, I show that the terms should not be used as synonyms since they describe different aspects of behavioural variation.

    In paper II, I observe large individual variation in both personality traits and learning speed in both chicks and adult red junglefowl. Interestingly, learning performance does not correlate across tasks, contrasting what has been found in humans and rodents. Thus, individuals that learn rapidly in one task are not necessarily fast learners in another task. I observe a relationship between personality and cognition that is task- and age-dependent, in which exploration relates to learning speed, but in opposite directions for chicks compared to adult females. In paper III, I show that red junglefowl chicks that are more behaviourally flexible have a stronger preference for new generalised stimuli, than less behaviourally flexible chicks. Behavioural flexibility was associated with fearfulness, indicating variation in reactive-proactive coping styles. In paper IV, I show that early cognitive stimulation to some extent can affect adult personality, thus showing a causal relationship between personality and cognition. Not all personality traits were affected, which might depend on the type of cognitive stimulation chicks were exposed to.

    Important cognitive processes like perception and decision-making, can contain biases. One such bias is called judgment bias, which describes how individuals interpret ambiguous stimuli on a scale from positive to negative (optimism to pessimism). In paper V, I show that alteration of emotional state can influence such biases. Here, unpredictable stress influence judgment bias negatively, when individuals are housed in simpler, but not in complex environments, suggesting that there is an effect of additive stress that lead to reduced optimism. Complexity instead seems to buffer against negative effects of stress, since individuals in complex environments remained optimistic after stress exposure. Furthermore, increased dopamine activity was associated with optimism in chicks. In paper VI, I find that aspects of personality associate with how chicks judge ambiguity. Highly active individuals are more likely to approach cues than less active individuals, and when approaching, individuals that are slow to approach ambiguous cues are more vigilant when assayed in personality assays. Vigilant individuals might be more worried and reactive, which suggest that emotional traits can influence responses in a judgment bias task.

    Taken together, I show consistent behavioural differences among individuals describing personality and coping styles, and variation in cognition. I show that these traits are related, and that there is an interplay between them, in which cognition can influence personality, and vice versa. I further show that judgment may be affected by the individual’s current affective state and personality. Thus, I show a complex relationship between personality and cognition that in combination with environmental effects can help explain behavioural variation.

    List of papers
    1. A comparison of animal personality and coping styles in the red junglefowl
    Open this publication in new window or tab >>A comparison of animal personality and coping styles in the red junglefowl
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    2017 (English)In: Animal Behaviour, ISSN 0003-3472, E-ISSN 1095-8282, Vol. 130, p. 209-220Article in journal (Refereed) Published
    Abstract [en]

    There is an increased focus in biology on consistent behavioural variation. Several terms are used to describe this variation, including animal personality and coping style. Both terms describe between individual consistency in behavioural variation; however, they differ in the behavioural assays typically used, the expected distribution of response variables, and whether they incorporate variation in behavioural flexibility. Despite these differences, the terms are often used interchangeably. We conducted experiments using juvenile and adult red junglefowl, Gallus gallus, as subjects to explore the degree to which animal personality and coping styles overlap. We demonstrate that animal personality and coping styles can be described in this species, and that shyer individuals had more flexible responses, as expected for coping styles. Behavioural responses from both personality and coping style assays had continuous distributions, and were not clearly separated into two types. Behavioural traits were not correlated and, hence, there was no evidence of a behavioural syndrome. Further, behavioural responses obtained in personality assays did not correlate with those from coping style tests. Animal personality and coping styles are therefore not synonymous in the red junglefowl. We suggest that the terms animal personality and coping style are not equivalent and should not be used interchangeably. (C) 2017 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

    Place, publisher, year, edition, pages
    ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2017
    Keywords
    boldness e; xploration; Gallus gallus; individual differences; stress coping
    National Category
    Behavioral Sciences Biology
    Identifiers
    urn:nbn:se:liu:diva-139903 (URN)10.1016/j.anbehav.2017.06.024 (DOI)000406939400022 ()
    Note

    Funding Agencies|Royal Swedish Academy of Sciences; Swedish Research Council; ERC (Advanced Research Grant Genewell); LiU programme for Future research leaders; Swedish research council Formas

    Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2017-09-13
    2. Early experience affects adult personality in the red junglefowl: a role for cognitive stimulation?
    Open this publication in new window or tab >>Early experience affects adult personality in the red junglefowl: a role for cognitive stimulation?
    Show others...
    2017 (English)In: Behavioural Processes, ISSN 0376-6357, E-ISSN 1872-8308, Vol. 134, p. 78-86Article in journal (Refereed) Published
    Abstract [en]

    Despite intense research efforts, biologists are still puzzled by the existence of animal personality. While recent studies support a link between cognition and personality, the directionality of this relationship still needs to be clarified. Early-life experiences can affect adult behaviour, and among these, cognitive stimulation has been suggested theoretically to influence personality. Yet, the influence of early cognitive stimulation has rarely been explored in empirical investigations of animal behaviour and personality. We investigated the effect of early cognitive stimulation on adult personality in the red junglefowl (Gallus gallus). To this end, we assessed adult behaviour across a number of personality assays and compared behaviour of individuals previously exposed to a series of learning tasks as chicks, with that of control individuals lacking this experience. We found that individuals exposed to early stimulation as adults were more vigilant and performed fewer escape attempts in personality assays. Other behaviours describing personality traits in the fowl were not affected. We conclude that our results support the hypothesis that early stimulation can affect aspects of adult behaviour and personality, suggesting a hitherto underappreciated causality link between cognition and personality. Future research should aim to confirm these findings and resolve their underlying dynamics and proximate mechanisms.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    Developmental plasticity, Boldness, Exploration, Gallus gallus, Juvenile learning, Neophobia, Vigilance
    National Category
    Behavioral Sciences Biology
    Identifiers
    urn:nbn:se:liu:diva-131304 (URN)10.1016/j.beproc.2016.06.003 (DOI)000392893600011 ()27329431 (PubMedID)
    Available from: 2016-09-13 Created: 2016-09-13 Last updated: 2018-03-28Bibliographically approved
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    The relationship between personality and cognitionin the fowl, Gallus gallus
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  • 1768.
    Zidar, Josefina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Balogh, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Favati, Anna
    Stockholm University, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Leimar, Olof
    Stockholm University, Sweden.
    Lovlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    A comparison of animal personality and coping styles in the red junglefowl2017In: Animal Behaviour, ISSN 0003-3472, E-ISSN 1095-8282, Vol. 130, p. 209-220Article in journal (Refereed)
    Abstract [en]

    There is an increased focus in biology on consistent behavioural variation. Several terms are used to describe this variation, including animal personality and coping style. Both terms describe between individual consistency in behavioural variation; however, they differ in the behavioural assays typically used, the expected distribution of response variables, and whether they incorporate variation in behavioural flexibility. Despite these differences, the terms are often used interchangeably. We conducted experiments using juvenile and adult red junglefowl, Gallus gallus, as subjects to explore the degree to which animal personality and coping styles overlap. We demonstrate that animal personality and coping styles can be described in this species, and that shyer individuals had more flexible responses, as expected for coping styles. Behavioural responses from both personality and coping style assays had continuous distributions, and were not clearly separated into two types. Behavioural traits were not correlated and, hence, there was no evidence of a behavioural syndrome. Further, behavioural responses obtained in personality assays did not correlate with those from coping style tests. Animal personality and coping styles are therefore not synonymous in the red junglefowl. We suggest that the terms animal personality and coping style are not equivalent and should not be used interchangeably. (C) 2017 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

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    fulltext
  • 1769.
    Zidar, Josefina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Balogh, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Stockholm Univ, Sweden.
    Favati, Anna
    Stockholm Univ, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Leimar, Olof
    Stockholm Univ, Sweden.
    Sorato, Enrico
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lovlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    The relationship between learning speed and personality is age- and task-dependent in red junglefowl2018In: Behavioral Ecology and Sociobiology, ISSN 0340-5443, E-ISSN 1432-0762, Vol. 72, no 10, article id UNSP 168Article in journal (Refereed)
    Abstract [en]

    Cognition is fundamental to animals lives and an important source of phenotypic variation. Nevertheless, research on individual variation in animal cognition is still limited. Further, although individual cognitive abilities have been suggested to be linked to personality (i.e., consistent behavioral differences among individuals), few studies have linked performance across multiple cognitive tasks to personality traits. Thus, the interplays between cognition and personality are still unclear. We therefore investigated the relationships between an important aspect of cognition, learning, and personality, by exposing young and adult red junglefowl (Gallus gallus) to multiple learning tasks (discriminative, reversal, and spatial learning) and personality assays (novel arena, novel object, and tonic immobility). Learning speed was not correlated across learning tasks, and learning speed in discrimination and spatial learning tasks did not co-vary with personality. However, learning speed in reversal tasks was associated with individual variation in exploration, and in an age-dependent manner. More explorative chicks learned the reversal task faster than less explorative ones, while the opposite association was found for adult females (learning speed could not be assayed in adult males). In the same reversal tasks, we also observed a sex difference in learning speed of chicks, with females learning faster than males. Our results suggest that the relationship between cognition and personality is complex, as shown by its task- and age-dependence, and encourage further investigation of the causality and dynamics of this relationship.Significance statementIn the ancestor of todays chickens, the red junglefowl, we explored how personality and cognition relate by exposing both chicks and adults to several learning tasks and personality assays. Our birds differed in personality and learning speed, while fast learners in one task did not necessarily learn fast in another (i.e., there were no overall smarter birds). Exploration correlated with learning speed in the more complex task of reversal learning: faster exploring chicks, but slower exploring adult females, learned faster, compared to less explorative birds. Other aspects of cognition and personality did not correlate. Our results suggest that cognition and personality are related, and that the relationship can differ depending on task and age of the animal.

  • 1770.
    Zidar, Josefina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Balogh, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Stockholm Univ, Sweden.
    Leimar, Olof
    Stockholm Univ, Sweden.
    Lovlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Generalization of learned preferences covaries with behavioral flexibility in red junglefowl chicks2019In: Behavioral Ecology, ISSN 1045-2249, E-ISSN 1465-7279, Vol. 30, no 5, p. 1375-1381Article in journal (Refereed)
    Abstract [en]

    The relationship between animal cognition and consistent among-individual behavioral differences (i.e., behavioral types, animal personality, or coping styles), has recently received increased research attention. Focus has mainly been on linking different behavioral types to performance in learning tasks. It has been suggested that behavioral differences could influence also how individuals use previously learnt information to generalize about new stimuli with similar properties. Nonetheless, this has rarely been empirically tested. Here, we therefore explore the possibility that individual variation in generalization is related to variation in behavioral types in red junglefowl chicks (Gallus gallus). We show that more behaviorally flexible chicks have a stronger preference for a novel stimulus that is intermediate between 2 learnt positive stimuli compared to more inflexible chicks. Thus, more flexible and inflexible chicks differ in how they generalize. Further, behavioral flexibility correlates with fearfulness, suggesting a coping style, supporting that variation in generalization is related to variation in behavioral types. How individuals generalize affects decision making and responses to novel situations or objects, and can thus have a broad influence on the life of an individual. Our results add to the growing body of evidence linking cognition to consistent behavioral differences.

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  • 1771.
    Zidar, Josefina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Campderrich, Irene
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden; Neiker-Tecnalia, Department of Animal Production, Vitoria-Gasteiz, Spain.
    Jansson, Emilie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wichman, Anette
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Winberg, Svante
    Department of Neuroscience, Uppsala Biomedical Centre BMC, Uppsala University, Uppsala, Sweden.
    Keeling, Linda
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Løvlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Environmental complexity buffers against stress-induced negative judgement bias in female chickens2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 5404Article in journal (Refereed)
    Abstract [en]

    Cognitive processes are often biased by emotions. In humans, affective disorders are accompanied by pessimistic judgement, while optimistic judgement is linked to emotional stability. Similar to humans, animals tend to interpret ambiguous stimuli negatively after experiencing stressful events, although the long-lasting impact on judgement bias has rarely been investigated. We measure judgement bias in female chicks (Gallus gallus domesticus) after exposure to cold stress, and before and after exposure to additional unpredictable stressors. Additionally, we explore if brain monoamines can explain differences in judgement bias. Chicks exposed to cold stress did not differ in judgement bias compared to controls, but showed sensitivity to additional stressors by having higher motivation for social reinstatement. Environmental complexity reduced stress-induced negative judgement bias, by maintaining an optimistic bias in individuals housed in complex conditions even after stress exposure. Moreover, judgement bias was related to dopamine turnover rate in mesencephalon, with higher activity in individuals that had a more optimistic response. These results demonstrate that environmental complexity can buffer against negative effects of additive stress and that dopamine relates to judgement bias in chicks. These results reveal that both internal and external factors can mediate emotionally biased judgement in animals, thus showing similarities to findings in humans.

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  • 1772.
    Zidar, Josefina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Sorato, Enrico
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Malmqvist, Ann-Marie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jansson, Emelie
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rosher, Charlotte
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Faculty of Life Sciences, University of Manchester, Manchester, UK.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Favati, Anna
    Department of Zoology, Stockholm University, Stockholm, Sweden.
    Løvlie, Hanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Early experience affects adult personality in the red junglefowl: a role for cognitive stimulation?2017In: Behavioural Processes, ISSN 0376-6357, E-ISSN 1872-8308, Vol. 134, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Despite intense research efforts, biologists are still puzzled by the existence of animal personality. While recent studies support a link between cognition and personality, the directionality of this relationship still needs to be clarified. Early-life experiences can affect adult behaviour, and among these, cognitive stimulation has been suggested theoretically to influence personality. Yet, the influence of early cognitive stimulation has rarely been explored in empirical investigations of animal behaviour and personality. We investigated the effect of early cognitive stimulation on adult personality in the red junglefowl (Gallus gallus). To this end, we assessed adult behaviour across a number of personality assays and compared behaviour of individuals previously exposed to a series of learning tasks as chicks, with that of control individuals lacking this experience. We found that individuals exposed to early stimulation as adults were more vigilant and performed fewer escape attempts in personality assays. Other behaviours describing personality traits in the fowl were not affected. We conclude that our results support the hypothesis that early stimulation can affect aspects of adult behaviour and personality, suggesting a hitherto underappreciated causality link between cognition and personality. Future research should aim to confirm these findings and resolve their underlying dynamics and proximate mechanisms.

    Download full text (pdf)
    fulltext
  • 1773.
    Ziels, Ryan
    et al.
    Linköping University, Biogas Research Center. Civil and Environmental Engineering, University of Washington, WA, USA.
    Karlsson, Anna
    Linköping University, Biogas Research Center. Scandinavian Biogas Fuels AB, Sweden.
    Beck, David A.C.
    Science Institute, University of Washington, WA, USA.
    Ejlertsson, Jörgen
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Biogas Research Center. Linköping University, Faculty of Arts and Sciences. Scandinavian Biogas Fuels AB, Sweden.
    Shakeri Yekta, Sepehr
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Biogas Research Center. Linköping University, Faculty of Arts and Sciences.
    Björn, Annika
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Biogas Research Center. Linköping University, Faculty of Arts and Sciences.
    Stensel, H. David
    Civil and Environmental Engineering, University of Washington, WA, USA.
    Svensson, Bo H.
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Biogas Research Center. Linköping University, Faculty of Arts and Sciences.
    Microbial community adaptation influences long-chain fatty acid conversion during anaerobic codigestion of fats, oils, and grease with municipal sludge2016In: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 103, p. 372-382Article in journal (Refereed)
    Abstract [en]

    Codigesting fats, oils, and greases with municipal wastewater sludge can greatly improve biomethanerecovery at wastewater treatment facilities. Process loading rates of fats, oils, and greases have beenpreviously tested with little knowledge of the digester microbial community structure, and high transientfat loadings have led to long chain fatty acid (LCFA) accumulation and digester upsets. This studyutilized recently-developed quantitative PCR assays for syntrophic LCFA-degrading bacteria along with16S amplicon sequencing to relate changes in microbial community structure to LCFA accumulationduring transient loading increases to an anaerobic codigester receiving waste restaurant oil andmunicipal wastewater sludge. The 16S rRNA gene concentration of the syntrophic b-oxidizing genusSyntrophomonas increased to ~15% of the Bacteria community in the codigester, but stayed below 3% inthe control digester that was fed only wastewater sludge. Methanosaeta and Methanospirillum were thedominant methanogenic genera enriched in the codigester, and together comprised over 80% of theArchaea community by the end of the experimental period. Constrained ordination showed that changesin the codigester Bacteria and Archaea community structures were related to measures of digester performance.Notably, the effluent LCFA concentration in the codigester was positively correlated to thespecific loading rate of waste oil normalized to the Syntrophomonas 16S rRNA concentration. Specificloading rates of 0e1.5 1012 g VS oil/16S gene copies-day resulted in LCFA concentrations below 30 mg/g TS, whereas LCFA accumulated up to 104 mg/g TS at higher transient loading rates. Based on thecommunity-dependent loading limitations found, enhanced biomethane production from high loadingsof fats, oils and greases can be achieved by promoting a higher biomass of slow-growing syntrophicconsortia, such as with longer digester solids retention times. This work also demonstrates the potentialfor controlling the loading rate of fats, oils, and greases based on the analysis of the codigester communitystructure, such as with quantitative PCR measurements of syntrophic LCFA-degrading bacteriaabundance.

  • 1774.
    Ziels, Ryan M.
    et al.
    University of Washington, WA 98195 USA.
    Beck, David A. C.
    University of Washington, WA 98195 USA; University of Washington, WA 98195 USA.
    Genero, Magalí Martí
    Linköping University, The Tema Institute, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Gough, Heidi L.
    University of Washington, WA 98195 USA.
    Stensel, H. David
    University of Washington, WA 98195 USA.
    Svensson, Bo
    Linköping University, The Tema Institute, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Monitoring the dynamics of syntrophic beta-oxidizing bacteria during anaerobic degradation of oleic acid by quantitative PCR2015In: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 91, no 4Article in journal (Refereed)
    Abstract [en]

    The ecophysiology of long-chain fatty acid-degrading syntrophic beta-oxidizing bacteria has been poorly understood due to a lack of quantitative abundance data. Here, TaqMan quantitative PCR (qPCR) assays targeting the 16S rRNA gene of the known mesophilic syntrophic beta-oxidizing bacterial genera Syntrophomonas and Syntrophus were developed and validated. Microbial community dynamics were followed using qPCR and Illumina-based high-throughput amplicon sequencing in triplicate methanogenic bioreactors subjected to five consecutive batch feedings of oleic acid. With repeated oleic acid feeding, the initial specific methane production rate significantly increased along with the relative abundances of Syntrophomonas and methanogenic archaea in the bioreactor communities. The novel qPCR assays showed that Syntrophomonas increased from 7 to 31% of the bacterial community 16S rRNA gene concentration, whereas that of Syntrophus decreased from 0.02 to less than 0.005%. High-throughput amplicon sequencing also revealed that Syntrophomonas became the dominant genus within the bioreactor microbiomes. These results suggest that increased specific mineralization rates of oleic acid were attributed to quantitative shifts within the microbial communities toward higher abundances of syntrophic beta-oxidizing bacteria and methanogenic archaea. The novel qPCR assays targeting syntrophic beta-oxidizing bacteria may thus serve as monitoring tools to indicate the fatty acid beta-oxidization potential of anaerobic digester communities.

  • 1775.
    Ziels, Ryan M.
    et al.
    Department of Civil Engineering, The University of British Columbia, Vancouver, BC, Canada.
    Svensson, Bo H
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Sundberg, Carina
    Linköping University, Department of Management and Engineering, Environmental Technology and Management. Linköping University, Faculty of Arts and Sciences.
    Larsson, Madeleine
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Karlsson, Anna
    Scandinavian Biogas Fuels AB, Stockholm, Sweden.
    Shakeri Yekta, Sepehr
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences. Linköping University, Biogas Research Center.
    Microbial rRNA gene expression and co-occurrence profiles associate with biokinetics and elemental composition in full-scale anaerobic digesters2018In: Microbial Biotechnology, ISSN 1751-7907, E-ISSN 1751-7915, Vol. 11, no 4, p. 694-709Article in journal (Refereed)
    Abstract [en]

    This study examined whether the abundance and expression of microbial 16S rRNA genes were associated with elemental concentrations and substrate conversion biokinetics in 20 full-scale anaerobic digesters, including seven municipal sewage sludge (SS) digesters and 13 industrial codigesters. SS digester contents had higher methane production rates from acetate, propionate and phenyl acetate compared to industrial codigesters. SS digesters and industrial codigesters were distinctly clustered based on their elemental concentrations, with higher concentrations of NH3-N, Cl, K and Na observed in codigesters. Amplicon sequencing of 16S rRNA genes and reverse-transcribed 16S rRNA revealed divergent grouping of microbial communities between mesophilic SS digesters, mesophilic codigesters and thermophilic digesters. Higher intradigester distances between Archaea 16S rRNA and rRNA gene profiles were observed in mesophilic codigesters, which also had the lowest acetate utilization biokinetics. Constrained ordination showed that microbial rRNA and rRNA gene profiles were significantly associated with maximum methane production rates from acetate, propionate, oleate and phenyl acetate, as well as concentrations of NH3-N, Fe, S, Mo and Ni. A co-occurrence network of rRNA gene expression confirmed the three main clusters of anaerobic digester communities based on active populations. Syntrophic and methanogenic taxa were highly represented within the subnetworks, indicating that obligate energy-sharing partnerships play critical roles in stabilizing the digester microbiome. Overall, these results provide new evidence showing that different feed substrates associate with different micronutrient compositions in anaerobic digesters, which in turn may influence microbial abundance, activity and function.

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  • 1776.
    Zook, Alexander E
    et al.
    Department of Ecology and Evolution, University of Chicago, United States.
    Eklöf, Anna
    Department of Ecology and Evolution, University of Chicago, United States.
    Jacob, Ute
    Institute for Hydrobiologie and Fisheries Science, University Hamburg, Germany.
    Allesina, Stefano
    Department of Ecology and Evolution, University of Chicago, United States; Computation Institute, University of Chicago, United States.
    Food webs: ordering species according to body size yields high degree of intervality2011In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 271, no 1, p. 106-113Article in journal (Refereed)
    Abstract [en]

    Food webs, the networks describing "who eats whom" in an ecosystem, are nearly interval, i.e. there is a way to order the species so that almost all the resources of each consumer are adjacent in the ordering. This feature has important consequences, as it means that the structure of food webs can be described using a single (or few) species' traits. Moreover, exploiting the quasi-intervality found in empirical webs can help build better models for food web structure. Here we investigate which species trait is a good proxy for ordering the species to produce quasi-interval orderings. We find that body size produces a significant degree of intervality in almost all food webs analyzed, although it does not match the maximum intervality for the networks. There is also a great variability between webs. Other orderings based on trophic levels produce a lower level of intervality. Finally, we extend the concept of intervality from predator-centered (in which resources are in intervals) to prey-centered (in which consumers are in intervals). In this case as well we find that body size yields a significant, but not maximal, level of intervality. These results show that body size is an important, although not perfect, trait that shapes species interactions in food webs. This has important implications for the formulation of simple models used to construct realistic representations of food webs.

  • 1777.
    Zou, Huiyun
    et al.
    Shandong Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Sun, Mingli
    Ctr Dis Prevent and Control, Peoples R China.
    Ottoson, Jakob
    Natl Food Agcy, Sweden.
    Li, Yubo
    Ctr Dis Prevent and Control, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Chi, Xiaohui
    Shandong Univ, Peoples R China.
    Ji, Xiang
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Lundborg, Cecilia Stalsby
    Karolinska Inst, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluating Dissemination Mechanisms of Antibiotic-Resistant Bacteria in Rural Environments in China by Using CTX-M-Producing Escherichia coli as an Indicator2019In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 25, no 7, p. 975-984Article in journal (Refereed)
    Abstract [en]

    It is becoming increasingly recognized that the environment plays an important role both in the emergence and in dissemination of antibiotic-resistant bacteria (ARB), Mechanisms and factors facilitating this development are, however, not yet well understood. The high detection rate of CTX-M genes in environmental sources provides an opportunity to explore this issue. In this study, 88 CTX-M-producing Escherichia coli were isolated from 30 pig feces samples from 30 pig farms and 201 environmental samples. CTX-M-producing E. coli was detected with the following frequencies in the different types of samples: pig feces, 73%; river water, 64%; river sediment, 52%; wastewater, 31%; drinking water, 23%; outlet sediment, 21%; soil, 17%; and vegetables, 4.4%. Dissemination of CTX-M-producing E. coli to different environmental matrices was evaluated by analyzing the genetic relatedness of isolates from different environmental sources, and putative transmission routes through bird feces, pig feces, drinking water, river sediment, river water, and wastewater were hypothesized. Dissemination through these routes is likely facilitated by anthropogenic activities and environmental factors. Wild birds as potential vectors for dissemination of CTX-M-producing E. coli have the capacity to spread ARB across long distances. Regional dissemination between different environmental matrices of CTX-M-producing E. coli increases the exposure risk of humans and animals in the area.

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    Evaluating Dissemination Mechanisms of Antibiotic-Resistant Bacteria in Rural Environments in China by Using CTX-M-Producing Escherichia coli as an Indicator
  • 1778.
    Zupan, Manja
    et al.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Box 7068, Uppsala, SE-750 07, Uppsala, Sweden.
    Buskas, Julia
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Keeling, Linda J.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Box 7068, Uppsala, SE-750 07, Uppsala, Sweden.
    Assessing positive emotional states in dogs using heart rate and heartrate variability2016In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 155, p. 102-111Article in journal (Refereed)
    Abstract [en]

    Since most animal species have been recognized as sentient beings, emotional state may be a good indicator ofwelfare in animals. The goal of this study was to manipulate the environment of nine beagle research dogs tohighlight physiological responses indicative of different emotional experiences. Stimuli were selected to be amore or a less positive food (meatball or food pellet) or social reward (familiar person or less familiar person).That all the stimuli were positive and of different reward value was confirmed in a runway motivation test.Dogs were tested individually while standing facing a display theatre where the different stimuli could beshown by lifting a shutter. The dogs approached and remained voluntarily in the test system. They were testedin four sessions (of 20 s each) for each of the four stimuli. A test session consisted of four presentation phases(1st exposure to stimulus, post exposure, 2nd exposure, and access to reward). Heart rate (HR) and heart ratevariability (HRV) responses were recorded during testing in the experimental room and also when lying restingin a quiet familiar room. A newmethod of ‘stitching’ short periods of HRV data together was used in the analysis.When testing different stimuli, no significant differenceswere observed in HR and LF:HF ratio (relative power inlow frequency (LF) and the high-frequency (HF) range), implying that the sympathetic tone was activated similarlyfor all the stimuli and may suggest that dogs were in a state of positive arousal. A decrease of HF was associatedwith the meatball stimulus compared to the food pellet and the reward phase (interacting with the personor eating the food) was associated with a decrease in HF and RMSSD (root mean square of successive differencesof inter-beat intervals) compared to the preceding phase (looking at the person or food). This suggests that parasympatheticdeactivation is associated with a more positive emotional state in the dog. A similar reduction in HFandRMSSDwas found in the test situation compared to the resting situation. This is congruentwith the expectedautonomic effects related to postural shift i.e. sympathetic activation and parasympathetic withdrawal, duringstanding versus lying, but it cannot explain the parasympathetic deactivation in response to the more positivestimuli since the dogs were always standing in the test situation.Wediscuss the systematic pattern of responses,which support that increased HRand LF:HF ratio are associatedwithemotional arousal, but add the newproposalthat a combined decrease inRMSSD and HFmay reflect a more positively valencedemotional state evenwhen anindividual is already in a positive psychological state.

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  • 1779.
    Zuse, Ann
    et al.
    Institute of Medicinal and Pharmaceutical Chemistry, Westphalian Wilhelms-University, Hittorfstrasse 58-62, D-48149 Münster, Germany; Manitoba Institute of Cell Biology, CancerCare Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, Canada.
    Prinz, Helge
    Institute of Medicinal and Pharmaceutical Chemistry, Westphalian Wilhelms-University, Hittorfstrasse 58-62, D-48149 Münster, Germany.
    Müller, Klaus
    Institute of Medicinal and Pharmaceutical Chemistry, Westphalian Wilhelms-University, Hittorfstrasse 58-62, D-48149 Münster, Germany.
    Schmidt, Peter
    Zentaris GmbH, Weismüllerstrasse 50, D-60314 Frankfurt, Germany.
    Günther, Eckhard G.
    Zentaris GmbH, Weismüllerstrasse 50, D-60314 Frankfurt, Germany.
    Schweizer, Frank
    Department of Chemistry, Univ. Manitoba, Winnipeg, Canada.
    Prehn, Jochen H.M.
    Department of Physiology and RCSI Research Institute, St. Stephen's Green, Dublin, Ireland.
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    9-benzylidene-naphtho[2,3-b]thiophen-4-ones and benzylidene-9(10H)-anthracenones as novel tubulin interacting agents with high apoptosis-inducing activity2007In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 575, no 1-3, p. 34-45Article in journal (Refereed)
    Abstract [en]

    Tubulin-binding 9-benzylidene-naphtho[2,3-b]thiophen-4-ones 1a and 1b and benzylidene-9(10H)-anthracenone 2 were evaluated for their ability to induce cell death. We examined the effect of the molecules on cell cycle progression, organization of microtubule networks, and apoptosis induction. As determined by flow cytometry, cancer cells were predominantly arrested in metaphase with 4N DNA before cell death occurred. By using indirect immunofluorescence techniques we visualized microtubule depolymerization recognizable by short microtubule fragments scattered around the nucleus. The incubation with 1a and 2 resulted in chromatin condensation, nuclear fragmentation, and cell shrinkage, which are, among others, typical features of apoptotic cell death. Furthermore, time- and dose-dependent induction of apoptosis in SH-SY5Y cells was detected via cleavage of Ac-DEVD-AMC, a fluorigenic substrate for caspase-3. We observed a lower apoptotic activity in neuroblastoma cells overexpressing Bcl-xL, suggesting activation of the mitochondrial apoptosis pathway. Western blot analysis demonstrated that caspase-3, an apoptosis mediator, was activated in a time-dependent manner after exposure of SH-SY5Y cells to drugs 1a and 2. Taken together, the agents investigated in the present study display strong apoptosis-inducing activity and therefore show promise for the development of novel chemotherapeutics.

  • 1780. Zuse, Anne
    et al.
    Prinz, Helge
    Mueller, Klaus
    Prehn, Jochen
    Los, Marek Jan
    BioApplications Enterprises, Winnipeg, MB, Canada; Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Design of novel small molecule inhibitors of tubulin polymerization with high apoptosis-inclucing activity2007In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 6, no 12, p. 3421S-3421SArticle in journal (Refereed)
  • 1781.
    Åberg, Elin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Turbiditet som ersättningsmått för totalfosforhalt i kustmynnande vattendrag i Östergötland2014Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Eutrophication is a major problem in the Baltic Sea, as a result of increased loading of nitrogen and phosphorus. In the coastal parts of Östergötland the soil largely consists of clay and contains high levels of phosphorus bound to clay particles. Erosion of the soil in agricultural areas makes the water turbid and transports phosphorus to the Baltic Sea. The aim of this project was to examine the relationship between phosphorus and turbidity in the coastal streams of Östergötland. The aim was also to evaluate the possibility to use turbidity as a surrogate measure for phosphorus. Water samples from 41 streams along the coast of Östergötland were collected once from each location 7 – 11 of April 2014. Variables examined were turbidity, total phosphorus, molybdate reactive phosphorus and water color (absorbance 420 nm). On average, particulate phosphorus made up 80 % of total phosphorus. The study showed a significant correlation between total phosphorus and turbidity (R2adj=0.879, P<0.01, linear regression). Water color was not correlated with total phosphorus. A multiple regression with turbidity and water color as independent variables resulted in a slightly improved model (R2adj = 0,886), but was regarded as not meaningful considering the additional efforts. The conclusion of the project is that is it possible to use turbidity as a surrogate measure in these streams. 

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  • 1782.
    Åkesson, Anna
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Alternativ modell för miljöundervisning i dagens gymnasieskola - modellekosystem2011Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Studies show that today's students are worried about the future and the increasing climate change. A survey made by the Swedish National Agency for Education about environmental education shows that approximately half of the surveyed secondary school teachers are not engaged in teaching in the field. This study describes an alternative model for teaching environmental issues. Students are by the modeling of ecosystem given an opportunity to deepen their understanding of climate change associated with the exploitation of top predators. This is a realistic problem, numerous studies show that today's ecosystems are exposed to a variety of stressors, with the origin of climate change, and the exploitation of top predators can lead to serious consequences with extinction as a result. The model used in this study is a generalized Lotka-Volterra model which works as an analytical tool. The Swedish National Agency for Education emphasizes the role of mathematics as interdisciplinary tools and model ecosystem gives students the opportunity to use math skills in a real scenario. The study also investigated how much exploitation top predators can be exposed to in line with increased climate change. The research sites include three-and four-species system of marine and terrestrial environments. The results show that the exploitation must be reduced in line with increased climate-caused changes in all cases, except terrestrial three-species system exposed to changes in interaction strengths.

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    Exjobb-modellekosystem
  • 1783.
    Åkesson, Julia
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics.
    Robust Community Predictions of Hubs in Gene Regulatory Networks2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Many diseases, such as cardiovascular diseases, cancer and diabetes, originate from several malfunctions in biological systems. The human body is regulated by a wide range of biological systems, composed of biological entities interacting in complex networks, responsible for carrying out specific functions. Some parts of the networks, such as hubs serving as master regulators, are more important for maintaining a function. To find the cause of diseases, where hubs are possible disease regulators, it is critical to know the structure of these biological systems. Such structures can be reverse engineered from high-throughput data with measured levels of biological entities. However, the complexity of biological systems makes inferring their structure a complicated task, demanding the use of computational methods, called network inference methods. Today, many network inference methods have been developed, that predicts the interactions of biological networks, with varying degree of success. In the DREAM5 challenge 35 network inference methods were evaluated on how well interactions in gene regulatory networks (GRNs) were predicted. Herein, in contrast to the DREAM5 challenge, we have evaluated network inference methods’ ability to predict hubs in GRNs. In accordance with the DREAM5 challenge, different methods performed the best on different data sets. Moreover, we discovered that network inference methods were not able to identify hubs from groups of similarly expressed genes. Also, we noticed that hubs in GRNs had a distinct expression in the data, leading to the development of a new method (the PCA method) for the prediction of hubs. Furthermore, the DREAM5 challenge showed that community predictions, combining the predictions from many network inference methods, resulted in more robust predictions of interactions. Herein, the community approach was applied on predicting hubs, with the conclusion that community predictions is the more robust approach. However, we also concluded that it was enough to combine 6-7 network inference methods to achieve robust predictions of hubs.

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  • 1784.
    Årevall, Jonatan
    Linköping University, Department of Physics, Chemistry and Biology.
    Klimatinducerade fenologiförändringar och dess effekter i näringsväven2011Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The climate affects animal populations through several processes. These processes includereproduction, phenology and the success of hunting. By influencing the phenology of species theclimate also affects the way species interact. If a climate-induced phenology change promotes abasal species to bud earlier in the spring for example, this will affect the links to other species inthe food web due to a time lag in the tropic levels above. This dependence, that a predator has tobeing synchronous to its prey, is called the match/mismatch hypothesis (MMH). Studies haveindicated that species higher up in the food web adapt slower than species lower in the food webwith shorter generation times (which creates a temporal mismatch).A climate-induced phenology change in basal species could therefore be expected to affect thedensities and extinction rates of species higher up in the food web.In this study a declining conversion efficiency for predators was used to model the effects ofclimate change on triangular food webs with three trophic levels. This was done by using ageneralized Lotka-Volterra model. The results indicate that, in a food web with three trophiclevels, the densities of herbivores and carnivores drops in response to an increased change ofclimate. The extinction rates of carnivores also increase rapidly in response to an increasedclimate change.

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  • 1785.
    Årevall, Jonatan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Early, Regan
    Univ Exeter Penryn Campus, England.
    Estrada, Alba
    Oviedo Univ Campus Mieres, Spain.
    Wennergren, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Eklöf, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Conditions for successful range shifts under climate change: The role of species dispersal and landscape configuration2018In: Diversity & distributions: A journal of biological invasions and biodiversity, ISSN 1366-9516, E-ISSN 1472-4642, Vol. 24, no 11, p. 1598-1611Article in journal (Refereed)
    Abstract [en]

    Aim: Ongoing climate change is currently modifying the geographical location of areas that are climatically suitable for species. Understanding a species ability to successfully shift its geographical range would allow us to assess extinction risks and predict future community compositions. We investigate how habitat configuration impedes or promotes climate-driven range shifts, given different speeds of climate change and dispersal abilities. Location: Theoretical, but illustrated with European examples. Methods: We model how a species ability to track a directional shift in climatic conditions is affected by (a) species dispersal abilities; (b) speed of climatic shift; and (c) spatial arrangement of the habitat. Our modelling framework includes within-and between-patch population dynamics and uses ecologically realistic habitat distributions and dispersal scenarios (verified with data from a set of European mammal species) and, as such, is an improvement of classical range shift models. Result: In landscapes with a homogeneous distribution of suitable habitats, all but the least dispersive species will be able to range shift. However, species with high dispersal ability will have lower population densities after range shift. In heterogeneous landscapes species ability to range shift is far more variable and heavily dependent on the habitat configuration. This means that landscape configuration in combination with the speed of climate change and species dispersal abilities give rise to nonlinear effects on population sizes and survival after a climatic shift. Main conclusions: Our analyses point out the importance of accounting for the interplay of species dispersal and the landscape configuration when estimating future climate impact on species. These results link ecologically important attributes of both species and their landscapes to outcomes of species range shift, and thereby long-term persistence of ecological communities.

  • 1786.
    Åström, Therese
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Betydelsen av skogskontinuitet och egenskaper hos gran för förekomst av Lecanactis abietina2013Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [sv]

    Skyddandet av gamla skogar med höga naturvärden är en viktig del i bevarandet av den biologiska mångfalden. För att kunna lokalisera och kvalitetsbedöma skogar med höga naturvärden används signalarter. En av dessa signalarter är Lecanactis abietina, gammelgranslav. Syftet med denna studie är att identifiera vilka faktorer som påverkar förekomst av signalarten L. abietina och täckningsgraden av apothecier. Studien utfördes i Ycke, Ullstämma och Säby Västerskog, vilka är naturreservat av olika ålder i Linköpings kommun, Östergötlands län. I de studerade områdena undersöktes samtliga granar med en diameter över 5 cm. Granarnas diameter och skuggning mättes, vid förekomst av L. abietina undersöktes förekomsten av apothecier, lavens täckningsgrad, maxhöjd och i vilka väderstreck laven förekom. Ett mindre urval av granarna borrades och ålderbestämdes. Resultatet visar att faktorerna som påverkar förekomst av L. abietina och täckningsgraden av apothecier främst är, skoglig kontinuitet i området, samt granarnas diameter och ålder. Resultaten från denna studie styrker användandet av L. abietina som lämplig indikatorart i Östergötland då lavens förekomst och spridning tydligt  speglade skogens kontinuitet (störst förekomst i de äldsta reservaten) och trädens egenskaper. Studien visar även att enbart förekomst inte räcker för att påvisa skog med höga naturvärden, utan de viktigaste faktorerna var förekomst av fertil lav, lavens täckningsgrad och frekvens på granar. Studien visar även att bevarandet av skogar med lång kontinuitet och förekomst av stora och gamla träd är viktigt för förekomsten av L. abietina.

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    Therese Åström
  • 1787.
    Öberg, Elisabet
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Non-fused Phospholes as Fluorescent Probes for Imaging of Lipid Droplets in Living Cells2017In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 5, article id 28Article in journal (Refereed)
    Abstract [en]

    Molecular tools for fluorescent imaging of specific compartments in cells are essential for understanding the function and activity of cells. Here, we report the synthesis of a series of pyridyl- and thienyl-substituted phospholes and the evaluation of these dyes for fluorescent imaging of cells. The thienyl-substituted phospholes proved to be successful for staining of cultured normal and malignant cells due to their fluorescent properties and low toxicity. Co-staining experiments demonstrated that these probes target lipid droplets, which are, lipid-storage organelles found in the cytosol of nearly all cell types. Our findings confirm that thienyl-substituted phospholes can be utilized as fluorescent tools for vital staining of cells, and we foresee that these fluorescent dyes might be used in studies to unravel the roles that lipid droplets play in cellular physiology and in diseases.

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  • 1788.
    Ödling, Sara
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Is there a correlation between the nutrient content and variation in the HvNAM-2 gene in Hordeum vulgare?2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Barley is one of the most important cereal crops in the world and a better understanding of the factors that regulates the nutrient content in the grain is of high interest. The industrial breeding during the last century has led to bigger yield but possibly a decrease in nutrient content. In wheat, the NAM-B1 gene is a well-studied gene that affects the grain protein and micronutrient content. Two orthologue genes in barley HvNAM-1 and HvNAM-2 are candidate genes to play a similar role in the barley senescence process.

    I have looked for a correlation between the diversity in the HvNAM-2 gene and nutrient content in 37 Nordic barley accessions. The samples were sequenced and then aligned and analyzed for variation. I found three haplotypes which were compared in nutrient content and in micronutrient content. No significant difference between the haplotypes was found, which can be due to small sample size or that no correlation exists between the grain protein content and the HvNAM-2 gene variation. Significant correlation was however found between the nitrogen content and the micronutrient contents that indicate that the pathways of all the nutrients’ mobilizations are tightly coupled. For future research a bigger number of accessions, preferably at least 100, need to be analyzed to be able to give any conclusions. The molecular mechanisms in the cells during senescence also need further investigation.

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  • 1789.
    Östensson, Frida
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Grain protein content and its assocoation with the NAC-protein genes HvNAM1 and HvNAM2 in Nordic barley2016Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Hunger is a problem faced by many people all over the world, and as the population grows, so does the need for food such as cereals. Because of this, the need for food with higher protein and nutrient content will be increasingly important. NAM-B1, a NAC-protein gene in wheat, has been shown to control the grain protein content and nutrient values, as well as senescence. In barley, two orthologous genes have been found, HvNAM1 and HvNAM2. This study focuses on Nordic barley accessions and how haplotypes of HvNAM1 and HvNAM2 correlate to the grain protein content (GPC) and nutrient content. No correlations between the different haplotypes of the HvNAM genes and the nutrient content and GPC were found. No differences in nutrient content and GPC were found in Nordic accessions originating from Sweden, Norway, Finland, or Denmark, nor were differences found for improvements status groups or for six-row barley and two-row barley. The Nordic accessions were shown to generally have high GPC when compared to control groups Karl and Lewis. However, even if the results of this study indicate that the HvNAM genes do not have major effects on the nutrient contents or GPC, Nordic barley might still be good material for plant improvement. Other factors such as other genes, environmental effects, and gene expression should therefore be investigated.

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  • 1790.
    Österberg, Emmy
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Ro52: Structure and interactions of constructs of RING and B-box2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The ubiquitination process is vital to maintain the protein homeostasis in the cell. With high specificity it regulates degradation of proteins by tagging them with a small protein called ubiquitin. Four proteins are involved to perform the process and in this thesis one of these proteins is studied. This protein is called Ro52 and belongs to the TRIM protein family. It posses E3 ligase activity because of a N-terminal RING-domain and therefore it is responsible for the last step in the ubiquitination process. The structure of Ro52 is not totally solved and the function of the protein’s four domains is not fully understood.

    In this thesis three constructs of two domains from Ro52 (RING and B-box) is investigated by circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy and auto-ubiquitination assay by Western blot. The goal was to gain deeper insight in structural and functional properties of these domains.

    In the end only two constructs were investigated because of time limitations. It was shown by NMR that one construct has similar structure as the wild type but lower stability, possibly due to shorter N-terminal region. Comparison of the results from CD measurements showed that the constructs were well structured but did not reveal any significant differences in secondary structure between the constructs. Functional analysis by Western blot encountered unexpected problems and no results were obtained.

    The current thesis provides a basis for further investigation of variant constructs jointly expressing the RING-B-box domains, and shows that even small changes may alter structure and stability in ways that might affect functional properties. 

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    Ro52: Structure and interactions of constructs of RING and B-box
  • 1791.
    Österman, Hanna
    Linköping University, Department of Physics, Chemistry and Biology.
    Olfactory performance and neuropathology in the Tg6799 strain of Alzheimer’s disease model mice2010Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    The present study evaluated olfactory and cognitive abilities of the Tg6799 (also called 5xFAD) strain of Alzheimer’s disease (AD) model mice of two different age groups (2-3 and 8-10 months of age), and one group of healthy control mice (9-10 months). Employment of an operant conditioning paradigm using an automated olfactometer, an olfactory habituation/dishabituation test and a spatial learning test with non olfactory cues resulted in data showing that the 5xFAD mice develop olfactory impairments already at 2-3 months of age. The impairments consisted in a robust impairment in olfactory sensitivity, decreased responsiveness to novel odors and an inability to discriminate between enantiomeric odor molecules in the 5xFAD mice compared to control mice. Spatial learning deficits were also detected at this age, suggesting that cognitive functions were also affected. No differences in magnitude of the olfactory or spatial learning impairments could be detected between the age groups of model mice tested. Histological examination of development and presence of amyloid β (Aβ) plaques in the brains showed that plaques develop mainly between the ages of 3 and 8 months. This indicates that soluble Aβ rather than the formation of plaques might be responsible for the olfactory impairment and spatial learning impairments found. By 10 months of age plaque load of the 5xFAD mice was massive. The results of the present study clearly show that the 5xFAD strain might be suitable for research on human AD with regard to the early onset of olfactory impairments.

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    Olfactory performance and neuropathology in the Tg6799 strain of Alzheimer’s disease model mice
  • 1792.
    Österman, Hanna
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lindgren, Isa
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Lindström, Tom
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Chronic hypoxia during development does not trigger pathologic remodeling of the chicken embryonic heart but reduces cardiomyocyte number2015In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 309, no 10, p. R1204-R1214Article in journal (Refereed)
    Abstract [en]

    Fetal growth restriction programs an increased risk of cardiovascular disease in adulthood, but the actual mechanisms of this developmental programming are not fully understood. Previous studies in mammalian models suggest that hearts of growth-restricted fetuses have reduced cardiomyocyte number due to reduced proliferation and premature cardiomyocyte maturation. Chicken embryos incubated under chronic hypoxia are also growth-restricted, have smaller hearts, and show signs of cardiac insufficiency posthatching. The aim of the present study was to investigate how chronic hypoxia (14% O-2) during development affects cardiomyocyte mass and how myocardial structure is altered. Hypoxic incubation reproduced the well-characterized embryonic growth restriction and an increased ventricle-to-body mass ratio (at E11, E15, E17, and E19) with reduced absolute heart mass only at E19. Cell density, apoptosis, and cardiomyocyte size were insensitive to hypoxia at E15 and E19, and no signs of ventricular wall remodeling or myocardial fibrosis were detected. Bayesian modeling provided strong support for hypoxia affecting absolute mass and proliferation rates at E15, indicating that the growth impairment, at least partly, occurs earlier in development. Neither E15 nor E19 hearts contained binucleated cardiomyocytes, indicating that fetal hypoxia does not trigger early maturation of cardiomyocytes in the chicken, which contrasts with previous results from hypoxic rat pups. In conclusion, prenatal hypoxia in the chick embryo results in a reduction in the number of cardiomyocytes without inducing ventricular remodeling, cell hypertrophy, or premature cardiomyocyte maturation.

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