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  • 251.
    Brengdahl, Martin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Kimber, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Maguire-Baxter, Jack
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Malacrinò, Antonino
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Friberg, Urban
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Genetic Quality Affects the Rate of Male and Female Reproductive Aging Differently in Drosophila melanogaster2018In: American Naturalist, ISSN 0003-0147, E-ISSN 1537-5323, Vol. 192, no 6, p. 761-772Article in journal (Refereed)
    Abstract [en]

    Males and females often maximize fitness by pursuing different reproductive strategies, with males commonly assumed to benefit more from increased resource allocation into current reproduction. Such investment should trade off with somatic maintenance and may explain why males frequently live shorter than females. It also predicts that males should experience faster reproductive aging. Here we investigate whether reproductive aging and life span respond to condition differently in male and female Drosophila melanogaster, as predicted if sexual selection has shaped male and female resource-allocation patterns. We manipulate condition through genetic quality by comparing individuals inbred or outbred for a major autosome. While genetic quality had a similar effect on condition in both sexes, condition had a much larger general effect on male reproductive output than on female reproductive output, as expected when sexual selection on vigor acts more strongly on males. We find no differences in reproductive aging between the sexes in low condition, but in high condition reproductive aging is relatively faster in males. No corresponding sex-specific change was found for life span. The sex difference in reproductive aging appearing in high condition was specifically due to a decreased aging rate in females rather than any change in males. Our results suggest that females age slower than males in high condition primarily because sexual selection has favored sex differences in resource allocation under high condition, with females allocating relatively more toward somatic maintenance than males.

  • 252.
    Brian, Björn
    Linköping University, The Department of Physics, Chemistry and Biology.
    Microarray Technology for Kinetic Analysis of Vesicle Bound Receptor-Ligand Interactions2007Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    A proof-of-concept for a novel microarray used to study protein-ligand interaction in real-time using label-free detection is presented. Many of todays commercially available instruments lack the ability to immobilize membrane proteins. At the same time, the pharmaceutical industry develops drugs directed towards membrane-bound receptors. The need to study drug-target kinetics and to be able to screen for new medical substances is high. To study the biomolecular interactions in real-time, imaging surface plasmon resonance (iSPR) is used. A patterned sensor surface with hydrophobic barriers assisting in the piezodispensing of NeutrAvidin with complex-bound biotin-ssDNA is created. Histidine-tagged proteins are immobilized at the vesicle surface using divalent nitrilotriacetic acid. The concept of the vesicle immobilization, the protein-binding to vesicles and the protein-ligand interaction is initially studied using a Biacore instrument. The dissociation of the ligand IFNα2 from its receptor ifnar-2 (wt) are in accordance with the literature. In the imaging SPR experiments, it is found that the dissociation of IFNα2 from the ifnar-2 (wt) receptor is slower than expected, probably due to rebinding of the ligand. It is also found that imidazole is needed to avoid vesicle-vesicle interaction. The immobilization of proteins had to be done on-line i.e. when the vesicles were bound to the surface. Depending on the mixture of receptors at the vesicle surface the affinity for the ligand was changed. The results achieved were reproducible.

  • 253.
    Brodd, Louise
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Behavioural differences between and within retriever breeds2016Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    The retriever breeds have the same origin and have long been used as a gundog for hunting of game, mostly birds. However, recently the retriever breeds have become a popular pet and show dog. This have affected the breeding of the dogs as the same traits are not bred for a gundog and a pet or show dog. Breeds as the Labrador retriever consists of a field- and common-type. The aim of this study is to investigate any differences between and within five of the retriever breeds in behaviours as retrieving, search and game reaction. 64 dogs undergoing the field trial Description of Function- Retriever was video recorded and scores from 430 dogs that have undergone field trials was obtained. Both differences between and within breeds were found when analysing both the videos and scores. In the video analysis, the Flatcoated retriever showed the most retrieving behaviours and was the most passive. The Nova scotia duck tolling retriever was in both the video and score analyses the most active breed. The Labrador retriever scored high in game reaction. The field- and mixed-types had almost always higher scores in behaviours linked to hunting, compared to the common-type. This supports findings that recent selection in breeding have a larger effect on behaviour than the origin uses of the dogs.

  • 254.
    Brodd, Louise
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    The help-seeking behaviour of dogs (Canis familiaris)2014Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    During domestication, the dog( Canis familiaris), have become skilful in understanding human communication and also in communicating with humans. The wolf ( Canis lupus), is not as skilled with this interspecific communication. When dogs are faced with an unsolvable problem, they seek help from human by e.g. gazing at them. This behaviour has been studied and both age and breed group differences have been showed. In this study, we presented dogs with a task that consisted of a solvable and unsolvable problem in order to see if they gazed at their owner and/or an unfamiliar person for help. Although we did not find any difference in breed groups regarding gazing at humans, we did find that adult dogs (dogs older than 2 years) gazed more frequently at their owner and for a longer duration than adolescent dogs (6 months to 2 years). This may be because the adult dogs have more experience of this communication with humans, as they have lived longer with them. These findings empathize the bond between a dog and its owner that seems to grow stronger during the dogs’ life.

  • 255.
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Pro- and anti-inflammatory regulation of β2 integrin signalling in human neutrophils2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The body is under constant attack from pathogens trying to slip by our immune defence. If the barrier is breached, invading pathogens enter the tissues and cause inflammation. During this process neutrophils, constituting the first line of defence, leave the bloodstream and seek out and kill the invading pathogens. The mechanisms leading to activation of receptors on neutrophils must be closely orchestrated. Pro- and anti-inflammatory substances can influence the outcome of the inflammation process by affecting the involved players. If not well balanced, inflammatory diseases, such as atherosclerosis and rheumatoid arthritis, can be the outcome.

    The aim of this thesis was to elucidate the effect of pro- (fMLP, Leukotriene B4, and Interleukin-8) and anti- (lipoxins, aspirin and statins) inflammatory substances on the β2 integrins, mediating adhesion of neutrophils both under “normal” conditions and during coronary artery disease. More specifically, the effect of these substances on the β2 integrins were studied in regard to: i) the activity (i.e. affinity and avidity) of β2 integrins, ii) the signalling capacity of β2 integrins (i.e. detected as release of arachidonic acid, and the production of reactive oxygen species, and iii) the signal transduction mediated by the β2 integrins (i.e. phosphorylation of Pyk2).

    The pro-inflammatory substances belong to the family of chemoattractants that induces transmigration and chemotaxis. A hierarchy exists between the different family members; the end-target chemoattractants (e.g. fMLP) being more potent than intermediary chemoattractants (e.g. IL-8 and LTB4). It was found that intermediary chemoattractants regulate β2 integrins by mainly affecting the avidity of β2 integrins. End-target chemoattractants on the other hand, affected the β2 integrins by increasing the avidity and the affinity, as well as their signalling capacity.

    The anti-inflammatory substances used in this study were the exogenous aspirin and statins, and the endogenous lipoxins. In the presence of aspirin, stable analogues of lipoxin (i.e. epi-lipoxins) are formed in a trans-cellular process. Lipoxin inhibited the signalling capacity of β2 integrins mediated by intermediary chemoattractants, as well as the signal transduction induced by end-target chemoattractants. Moreover, the signalling capacity of β2 integrins in neutrophils from patients suffering from coronary artery disease (CAD) was impaired. Arachidonic acid, the precursor for both pro- and anti-inflammatory eicosanoid, induced an increase in the β2 integrin activity (both affinity and avidity), but had no effect on the signal transduction.

    In conclusion, different “roles” were observed for end-target and intermediary chemoattractants in the regulation of β2 integrins. The inhibitory effects of the anti-inflammatory lipoxins support earlier studies suggesting that these agents function as “stop signals” in inflammation. This is also confirmed by our findings in CAD patients, who have elevated levels of epi-lipoxins due to aspirin treatment. Moreover, Pyk2 was identified as a possible target for the inhibitory effect of anti-inflammatory drugs.

    List of papers
    1. Differential inside-out activation of β2 integrins by leukotriene B4 and fMLP in human neutrophils
    Open this publication in new window or tab >>Differential inside-out activation of β2 integrins by leukotriene B4 and fMLP in human neutrophils
    Show others...
    2004 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 300, no 2, p. 308-319Article in journal (Refereed) Published
    Abstract [en]

    We have investigated how LTB4, an endogenous chemoattractant encountered early in the inflammatory process, and fMLP, a bacteria-derived chemotactic peptide emanating from the site of infection, mediate inside-out regulation of the β2-integrin. The role of the two chemoattractants on β2-integrin avidity was investigated by measuring their effect on β2-integrin clustering and surface mobility, whereas their effect on β2-integrin affinity was measured by the expression of a high affinity epitope, a ligand-binding domain on β2-integrins, and by integrin binding to s-ICAM. We find that the two chemoattractants modulate the β2-integrin differently. LTB4 induces an increase in integrin clustering and surface mobility, but only a modest increase in integrin affinity. fMLP evokes a large increase in β2-integrin affinity as well as in clustering and mobility. Lipoxin, which acts as a stop signal for the functions mediated by pro-inflammatory agents, was used as a tool for further examining the inside-out mechanisms. While LTB4-induced integrin clustering and mobility were inhibited by lipoxin, only a minor inhibition of fMLP-induced β2-integrin avidity and no inhibition of integrin affinity were detected. The different modes of the inside-out regulation of β2-integrins suggest that distinct mechanisms are involved in the β2-integrin modulation induced by various chemoattractants.

    Keywords
    β2-Integrins, Cell adhesion, Chemotactic factors, Eicosanoids, Inflammation, Leukotriene B4, Lipoxins, Human Neutrophils, Signal transduction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14629 (URN)10.1016/j.yexcr.2004.07.015 (DOI)
    Available from: 2007-09-13 Created: 2007-09-13 Last updated: 2017-12-13Bibliographically approved
    2. LIpoxin A4 inhibits the fMet-Leu-Phe-induced, but not the β2 integrin-induced activation of the non-receptor tyrosine kinase Pyk2 in Human Leukemia 60 cells
    Open this publication in new window or tab >>LIpoxin A4 inhibits the fMet-Leu-Phe-induced, but not the β2 integrin-induced activation of the non-receptor tyrosine kinase Pyk2 in Human Leukemia 60 cells
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14630 (URN)
    Available from: 2007-09-13 Created: 2007-09-13 Last updated: 2010-01-13
    3. Inside-out regulated β2-integrin-induced release of arachidonic acid in Human Leukemia 60 cells
    Open this publication in new window or tab >>Inside-out regulated β2-integrin-induced release of arachidonic acid in Human Leukemia 60 cells
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14631 (URN)
    Available from: 2007-09-13 Created: 2007-09-13 Last updated: 2010-01-13
    4. Inactivation of Cdc42 is nessecary for depolymerization of phagosomal F-actin and subsequent phagosomal maturation
    Open this publication in new window or tab >>Inactivation of Cdc42 is nessecary for depolymerization of phagosomal F-actin and subsequent phagosomal maturation
    Show others...
    2007 (English)In: Journal of Immunology, ISSN 0022-1767, Vol. 178, no 11, p. 7357-7365Article in journal (Refereed) Published
    Abstract [en]

    Phagocytosis is a complex process involving the activation of various signaling pathways, such as the Rho GTPases, and the subsequent reorganization of the actin cytoskeleton. In neutrophils, Rac and Cdc42 are activated during phagocytosis but less is known about the involvement of these GTPases during the different stages of the phagocytic process. The aim of this study was to elucidate the role of Cdc42 in phagocytosis and the subsequent phagosomal maturation. Using a TAT-based protein transduction technique, we introduced dominant negative and constitutively active forms of Cdc42 into neutrophil-like HL60 (human leukemia) cells that were allowed to phagocytose IgG-opsonized yeast particles. Staining of cellular F-actin in cells transduced with constitutively active Cdc42 revealed that the activation of Cdc42 induced sustained accumulation of periphagosomal actin. Moreover, the fusion of azurophilic granules with the phagosomal membrane was prevented by the accumulated F-actin. In contrast, introducing dominant negative Cdc42 impaired the translocation per se of azurophilic granules to the periphagosomal area. These results show that efficient phagosomal maturation and the subsequent eradication of ingested microbes in human neutrophils is dependent on a strictly regulated Cdc42. To induce granule translocation, Cdc42 must be in its active state but has to be inactivated to allow depolymerization of the F-actin cage around the phagosome, a process essential for phagolysosome formation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14632 (URN)
    Available from: 2007-09-13 Created: 2007-09-13
    5. Neutrophil activation status in stable coronary artery disease.
    Open this publication in new window or tab >>Neutrophil activation status in stable coronary artery disease.
    Show others...
    2007 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 2, no 10, p. e1056-Article in journal (Refereed) Published
    Abstract [en]

    Background: During the last years, neutrophils have emerged as important players in atherogenesis. They are highly activated in peripheral blood of patients with unstable angina. Moreover, a primed state of circulating neutrophils has been proposed in patients with stable angina. Our aim was to investigate the neutrophil activation status in patients with stable coronary artery disease (CAD) at conventional drug treatment.

    Methodology and principal findings: Thirty patients with stable CAD and 30 healthy controls were included using a paired design. The neutrophil expression of CD18 and high-affinity state of CD11b was analysed by flow cytometry before and after stimulation with chemoattractants. Also, the production of reactive oxygen species (ROS) was determined by chemiluminescence. During basal conditions, the neutrophil expression of CD18 or high-affinity state of CD11b did not differ between patients and controls. Chemoattractants (Interleukin-8 and Leukotriene B(4)) did not increase either the expression or the amount of high-affinity CD11b/CD18-integrins in CAD patients compared to controls, and had no effect on the production of ROS. On the other hand, the ROS production in response to C3bi-opsonised yeast particles and the neutrophils' inherent capacity to produce ROS were both significantly decreased in patients.

    Conclusion/Significance: We could not find any evidence that neutrophils in patients with stable CAD were primed, i.e. more prone to activation, compared to cells from healthy controls. According to our data, the circulating neutrophils in CAD patients rather showed an impaired activation status. It remains to be elucidated whether the neutrophil dysfunction in CAD is mainly a marker of chronic disease, an atherogenic factor or a consequence of the drug treatment.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17246 (URN)10.1371/journal.pone.0001056 (DOI)17957240 (PubMedID)
    Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2010-01-14
  • 256.
    Brose, Ulrich
    et al.
    German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103, Leipzig, Germany 2 Faculty of Biology and Pharmacy, Institute of Ecology, Friedrich Schiller University Jena, 07743, Jena, Germany.
    Blanchard, Julia L.
    Institute for Marine and Antarctic Studies and Centre for Marine Socioecology, University of Tasmania, 20 Castray Esplanade, Battery Point TAS 7004 Australia.
    Eklöf, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Galiana, Nuria
    Ecological Networks and Global Change Group, Experimental Ecology Station, Centre National de la Recherche Scientifique, 09200, Moulis, France.
    Hartvig, Martin
    Center for Macroecology, Evolution and Climate, Natural History Museum of Denmark, University of Copenhagen, DK-2100, Copenhagen, Denmark 7 National Institute of Aquatic Resources, Technical University of Denmark, DK-2920, Charlottenlund, Denmark 8 Systemic Conservation Biology Group, J.F. Blumenbach Institute of Zoology and Anthropology, Georg-August University of Göttingen, 37073, Göttingen, Germany.
    Hirt, Myriam R.
    German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103, Leipzig, Germany 2 Faculty of Biology and Pharmacy, Institute of Ecology, Friedrich Schiller University Jena, 07743, Jena, Germany.
    Kalinkat, Gregor
    Department of Biology and Ecology of Fishes, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, 12587, Berlin, Germany 10 Department of Fish Ecology and Evolution, Eawag, 6047, Kastanienbaum, Switzerland.
    Nordström, MArie C.
    Environmental and Marine Biology, Åbo Akademi University, FI-20520, Åbo, Finland.
    O'Gorman, Eoin J.
    Imperial College London, Silwood Park Campus, Buckhurst Road, Ascot, Berkshire, SL5 7PY, UK.
    Rall, Björn C.
    German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, 04103, Leipzig, Germany 2 Faculty of Biology and Pharmacy, Institute of Ecology, Friedrich Schiller University Jena, 07743, Jena, Germany.
    Schneider, Florian D.
    Institut des Sciences de l’Evolution, Universit´e Montpellier, CNRS, IRD, EPHE, CC065, 34095, Montpellier Cedex 05, France.
    Thébault, Elisa
    Institute of Ecology and Environmental Sciences - Paris, UMR 7618 (UPMC, CNRS, IRD, INRA, UPEC, Paris Diderot), Universit´e Pierre et Marie Curie, 75005, Paris, France.
    Jacob, Ute
    Department of Biology, Institute for Hydrobiology and Fisheries Science, Center for Earth System Research and Sustainability (CEN), KlimaCampus, University of Hamburg, 22767, Hamburg, Germany.
    Predicting the consequences of species lossusing size-structured biodiversity approaches2017In: Biological Reviews, ISSN 1464-7931, E-ISSN 1469-185X, Vol. 92, no 2, p. 684-697Article, review/survey (Refereed)
    Abstract [en]

    Understanding the consequences of species loss in complex ecological communities is one of the great challenges in current biodiversity research. For a long time, this topic has been addressed by traditional biodiversity experiments. Most of these approaches treat species as trait-free, taxonomic units characterizing communities only by species number without accounting for species traits. However, extinctions do not occur at random as there is a clear correlation between extinction risk and species traits. In this review, we assume that large species will be most threatened by extinction and use novel allometric and size-spectrum concepts that include body mass as a primary species trait at the levels of populations and individuals, respectively, to re-assess three classic debates on the relationships between biodiversity and (i) food-web structural complexity, (ii) community dynamic stability, and (iii) ecosystem functioning. Contrasting current expectations, size-structured approaches suggest that the loss of large species, that typically exploit most resource species, may lead to future food webs that are less interwoven and more structured by chains of interactions and compartments. The disruption of natural body-mass distributions maintaining food-web stability may trigger avalanches of secondary extinctions and strong trophic cascades with expected knock-on effects on the functionality of the ecosystems. Therefore, we argue that it is crucial to take into account body size as a species trait when analysing the consequences of biodiversity loss for natural ecosystems. Applying size-structured approaches provides an integrative ecological concept that enables a better understanding of each species' unique role across communities and the causes and consequences of biodiversity loss.

  • 257.
    Brose, Ulrich
    et al.
    Technical University of Darmstadt, Germany.
    Pavao-Zuckerman, Mitchell
    University of Arizona, Tucson, Arizona, USA.
    Eklöf, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    Bengtsson, Janne
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Berg, Matty P.
    Vrije Universiteit Amsterdam, The Netherlands.
    Cousins, Steven H.
    Cranfield University, United Kingdom.
    Mulder, Christian
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    Verhoef, Herman A.
    Vrije Universiteit Amsterdam, The Netherlands.
    Wolters, Volkmar
    Justus-Liebig-University, Giessen, Germany.
    Spatial aspects of food webs2005In: Dynamic Food Webs: Multispecies Assemblages, Ecosystem Development and Environmental Change / [ed] P.C. deRuiter, V. Wolters & J.C. Moore, London, UK: Elsevier, 2005, Vol. 3, p. 463-469Conference paper (Refereed)
    Abstract [en]

    Aspects of spatial scale have until recently been largely ignored in empirical and theoretical food web studies (e.g., Cohen & Briand 1984, Martinez 1992, but see Bengtsson et al. 2002, Bengtsson & Berg, this book). Most ecologists tend to conceptualize and represent food webs as static representations of communities, depicting a community assemblage as sampled at a particular point in time, or highly aggregated trophic group composites over broader scales of time and space (Polis et al. 1996). Moreover, most researchers depict potential food webs, which contain all species sampled and all potential trophic links based on literature reviews, several sampling events, or laboratory feeding trials. In reality, however, not all these potential feeding links are realized as not all species co-occur, and not all samples in space or time can contain all species (Schoenly & Cohen 1991), hence, yielding a variance of food web architecture in space (Brose et al. 2004). In recent years, food web ecologists have recognized that food webs are open systems – that are influence by processes in adjacent systems – and spatially heterogeneous (Polis et al. 1996). This influence of adjacent systems can be bottom-up, due to allochthonous inputs of resources (Polis & Strong 1996, Huxel & McCann 1998, Mulder & De Zwart 2003), or top-down due to the regular or irregular presence of top predators (e.g., Post et al. 2000, Scheu 2001). However, without a clear understanding of the size of a system and a definition of its boundaries it is not possible to judge if flows are internal or driven by adjacent systems. Similarly, the importance of allochthony is only assessable when the balance of inputs and outputs are known relative to the scale and throughputs within the system itself. At the largest scale of the food web – the home range of a predator such as wolf, lion, shark or eagle of roughly 50 km2 to 300 km2 –the balance of inputs and outputs caused by wind and movement of water may be small compared to the total trophic flows within the home range of the large predator (Cousins 1990). Acknowledging these issues of space, Polis et al (1996) argued that progress toward the next phase of food web studies would require addressing spatial and temporal processes. Here, we present a conceptual framework with some nuclei about the role of space in food web ecology. Although we primarily address spatial aspects, this framework is linked to a more general concept of spatio-temporal scales of ecological research.

  • 258.
    Brunberg, Emma I
    et al.
    NORSØK – Norwegian Centre for Organic Agriculture, Tingvoll, Norway; NIBIO – Norwegian Institute for Bioeconomy Research, Tingvoll, Norway.
    Rodenburg, T Bas
    Behavioural Ecology Group, Wageningen University, Wageningen, Netherlands.
    Rydhmer, Lotta
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kjaer, Joergen B
    Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Celle, Germany,.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Keeling, Linda J
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens2016In: Frontiers in veterinary science, ISSN 2297-1769, Vol. 3, p. 1-15, article id 57Article in journal (Refereed)
    Abstract [en]

    Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain-gut-microbiota axis.

  • 259.
    Brusman, Anna-Lena
    Linköping University, The Department of Physics, Chemistry and Biology.
    Etiska aspekter av preimplantatorisk genetisk diagnostik och genterapi2007Independent thesis Advanced level (degree of Magister), 20 points / 30 hpStudent thesis
    Abstract [en]

    The research in the field of biotechnology is rapidly developing all over the world. Modern biotechnology offers unique opportunities, simultaneously as it gives rise to a number of ethical issues. Preimplantation genetic diagnosis (PGD), PGD/HLA (Human Leucocyte Antigen) and germline gene therapy (GLGT) are controversial techniques. PGD gives a possibility to identify a genetic disease prior to the embryo’s implantation in the uterus. PGD/HLA involves selecting an embryo with genes coding for a specific tissue type, so that the child to be born can act as a donor to an existing sibling who requires a stem cell transplant. GLGT seeks to eliminate or change “bad” genes.

    The purpose of this study is to investigate student’s ethical attitude concerning PGD, PGD/HLA and GLGT.

    The empirical study was based on focus group discussions. Four group interviews were made, with 15 participants in all. The students are taking courses in biology or religion.

    The result from the interviews shows that the ethical issues are difficult to have a definite opinion in, because there are possibilities and risks involved in all these techniques, according to the students. A central part of the discussion was devoted to human dignity and the moral status of the embryo. They also see risks such as bioterrorism, designing the perfect humans, economic interests, medical risks, among many other risks.

  • 260.
    Bröms Axelsson, Emilia
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Do we protect the right forests? – A case study of representativeness of protected forests in Östergötland, Sweden, and identification of tracts of value.2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Protected forests need to be a representative selection of the natural proportion of forest types, including distribution of productivity levels, age classes and nature types This is important for the possibility to preserve biodiversity. In addition, the protected areas has to be of sufficient size and not isolated from each other, to function as effective biodiversity preservers. The question is, how does it look in reality? The objective with this study was to get an overall picture of the current forest protection situation in Östergötland, Sweden, and how it has changed the last 60 years. Are all ecologically relevant forest habitat types represented in appropriate proportions in protected forests? To evaluate where the protected areas are located in relation to each other, a connectivity index was calculated for each patch of protected area. Together with a value for size, a value index was created and applied to all protected areas, and it turns out that the protected areas of Östergötland is not totally representative when it comes to nature types, age classes and levels of productivity.For example, there is an underrepresentation of both pine and spruce forests on high-productivity soils. However, areas with higher productivity levels have been protected over time. The age distribution seems to be skewed towards older forests in protected areas. There are some underrepresented nature types, as well as overrepresented ones in nature reserves, a small overrepresentation of unproductive impediments, and only spruce and mixed forests seems well connected in the landscape. The greatest differences in protected and unprotected forests is the productivity level, were focus should be on protecting higher productivity areas in order to succeed in preserving the biodiversity of forests as intended.

  • 261.
    Bröms Axelsson, Emilia
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Kloridutlakning från flygaska: möjligheten till en lokal hantering2014Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [en]

    In Sweden, there are limits to how much leachable substances waste must contain in order to be deposited as hazardous waste. Fly ash from waste incineration often end up over the limit, mainly due to the chloride content. Fly ash is therefore often deposited abroad. The purpose of this study was to investigate the possibility to handle fly ash locally. To clarify how the law is applied, environmental reports and permit documents from ten waste sites with permission to deposit fly ash were studied. In addition, a literature study was made to review the state of knowledge regarding the treatments of fly ash. The treatment methods are numerous, but are at different levels of commerciality. Among the treatments available there are both physical, chemical, biological, electrical and thermal variants. Many of the treatments (except for carbonation and microbial bioleaching) results in chloride levels below the limits. Several are however unrealistically expensive or generate wastewater with high levels of chloride that would need further treatment. Three plants out of the ten holding permits to deposit fly ash, have exemptions from the limit for chlorides. It's however difficult to see a common reasoning for allowing exemptions. In several cases there are sensitive receiving waters downstream from the landfill. One reason to be dispensed despite this sensitivity, may be the guidance that EPA issued. It is not formulated any specific concerns relating to chlorides. One handles therefore often high levels of chloride in the leachate as a dilution problem, not a leaching problem.

  • 262.
    Brüsin, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Influence of landscape scale and habitat distribution on individual bat species and bat species richness2013Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Habitat fragmentation is one of the most important factors affecting species extinction and biodiversity loss, Species habitat response expects to differ with habitat feature at different spatial scales and this study was to identify how bat diversity and individual bat species respond to different habitat amounts. The local bat species richness was observed in 156 different locations in Östergötland and the proportion of different habitats were calculated for circular areas with diameters ranging from 400 m. to 12 km. from each location. Although we found that the individual bat species responded differently to the amount of each habitat at different spatial scales, the bat species richness showed a decreasing response with increasing spatial scale. The strongest response of bat species richness to habitat characteristics was at a scale of 939 m.

  • 263.
    Bunkoczi, Gabor
    et al.
    University of Cambridge, England.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Read, Randy J.
    University of Cambridge, England.
    Local Error Estimates Dramatically Improve the Utility of Homology Models for Solving Crystal Structures by Molecular Replacement2015In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 23, no 2, p. 397-406Article in journal (Refereed)
    Abstract [en]

    Predicted structures submitted for CASP10 have been evaluated as molecular replacement models against the corresponding sets of structure factor amplitudes. It has been found that the log- likelihood gain score computed for each prediction correlates well with common structure quality indicators but is more sensitive when the accuracy of the models is high. In addition, it was observed that using coordinate error estimates submitted by predictors to weight the model can improve its utility in molecular replacement dramatically, and several groups have been identified who reliably provide accurate error estimates that could be used to extend the application of molecular replacement for low-homology cases.

  • 264.
    Bunnfors, Kalle
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Synthesis and electrochemical characterisation of processable polypyrrole boronic acid derivatives for carbohydrate binding2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Conducting polymers have been widely explored for many different purposes including sensing. In thisthesis the conducive properties of pyrrole and the carbohydrate binding properties of boronic acid iscombined to make a reagent-free detector for carbohydrates. The polymer is manufactured in form ofparticles in the μm scale to create a porous film which has a high surface to volume ratio.The material was characterised and the binding properties were evaluated for galactose and glucose.Proof of binding was found via both electrochemical methods and QCM-D. A correlation between R2 value and concentration of substrate was found which enables measurement of concentration of carbohydratesin unknown samples.

  • 265.
    Burek, C. J.
    et al.
    University of Münster, Germany.
    Roth, J.
    University of Münster, Germany.
    Koch, H. G.
    University of Münster, Germany.
    Harzer, K.
    University of Tübingen, Germany.
    Los, Marek Jan
    Department of Immunology and Cell Biology, University of Münster, Germany.
    Schulze-Osthoff, Klaus
    University of Münster, Germany .
    The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells2001In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 20, no 45, p. 6493-6502Article in journal (Refereed)
    Abstract [en]

    The activation of sphingomyelinases leading to the generation of ceramide has been implicated in various apoptotic pathways. However, the role of ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of ceramide in a genetic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic ceramidase. We demonstrate that Farber disease lymphocytes and fibroblasts underwent apoptosis induced by various stress stimuli, including staurosporine, anticancer drugs and gamma -irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rather similarly in Farber disease and control fibroblasts. Interestingly, Farber disease lymphoid cells underwent apoptosis induced by the CD95 death receptor more rapidly than control cells. Our data therefore suggest that ceramide does not play an essential role as a second messenger in stress-induced apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis.

  • 266.
    Burek, M.
    et al.
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Maddika, Subbareddy
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada .
    Burek, C. J.
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Daniel, P. T.
    Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany.
    Schulze-Osthoff, Klaus
    nstitute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany .
    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, .
    Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1dependent2006In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 25, no 15, p. 2213-2222Article in journal (Refereed)
    Abstract [en]

    Apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in transformed but not in normal cells, thus making it a promising candidate as a novel anticancer therapeutic. The mechanism of apoptin-induced apoptosis is largely unknown. Here, we report that contrary to previous assumptions, Bcl-2 and Bcl-x(L) inhibit apoptin-induced cell death in several tumor cell lines. In contrast, deficiency of Bax conferred resistance, whereas Bax expression sensitized cells to apoptin-induced death. Cell death induction by apoptin was associated with cytochrome c release from mitochondria as well as with caspase-3 and -7 activation. Benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad spectrum caspase inhibitor, was highly protective against apoptin-induced cell death. Apoptosis induced by apoptin required Apaf-1, as immortalized Apaf-1-deficient fibroblasts as well as tumor cells devoid of Apaf-1 were strongly protected. Thus, our data indicate that apoptin-induced apoptosis is not only Bcl-2- and caspase dependent, but also engages an Apaf-1 apoptosome-mediated mitochondrial death pathway.

  • 267.
    Burgevin, Lorraine
    et al.
    Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Friberg, Urban
    Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Maklakov, Alexei A.
    Department of Animal Ecology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Intersexual correlation for same-sex sexual behaviour in an insect2013In: Animal Behaviour, ISSN 0003-3472, E-ISSN 1095-8282, Vol. 85, no 4, p. 759-762Article in journal (Refereed)
    Abstract [en]

    Same-sex sexual behaviour is widespread across taxa and is particularly common in insects, in which up to 50% of copulation attempts by males are directed towards other males in some species. Research effort has focused on male-male same-sex behaviour and the prevailing theory is that benefits of high mating rate combined with poor sex discrimination explain the high incidence of male-male mounting. However, the evolution of female-female mounting is more enigmatic, since females typically do not mount males in order to mate. Using a full-sib design, we found an intersexual correlation for same-sex mounting in the beetle Callosobruchus maculatus. Variation in male-male mounting across families explained over 20% of variation in female-female mounting. Moreover, we found no evidence that same-sex behaviour was related to general activity level in either sex or carried a fitness cost to females. Taken together, our results suggest that female-female mounting is a relatively low-cost behaviour that may be maintained in the population via selection on males.

  • 268.
    Burman, Joseph
    et al.
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Box 102, 230 53 Alnarp, Sweden/Ecology Research Group, Canterbury Christ Church University, Canterbury, Kent, CT1 1QU, England, UK .
    Westerberg, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Ostrow, Suzanne
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Ryrholm, Nils
    University of Gävle, 801 76 Ga¨vle, Sweden.
    Bergman, Karl-Olof
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Winde, Inis
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences,Alnarp, Sweden, Department of Biology, Lund University, So¨lvegatan 37, 223 62 Lund, Sweden.
    Nyabuga, Franklin N.
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Box 102, 230 53 Alnarp, Sweden, Department of Biology, Lund University, So¨lvegatan 37, 223 62 Lund, Sweden.
    Larsson, Mattias C.
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Box 102, 230 53 Alnarp, Sweden.
    Milberg, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Revealing hidden species distribution with pheromones: the caseof Synanthedon vespiformis (Lepidoptera: Sesiidae) in Sweden2016In: Journal of Insect Conservation, ISSN 1366-638X, E-ISSN 1572-9753, Vol. 20, no 1, p. 11-21Article in journal (Refereed)
    Abstract [en]

    Synanthedon vespiformis L. (Lepidoptera:Sesiidae) is considered a rare insect in Sweden, discoveredin 1860, with only a few observations recorded until a sexpheromone attractant became available recently. This studydetails a national survey conducted using pheromones as asampling method for this species. Through pheromonetrapping we captured 439 specimens in Southern Sweden at77 sites, almost tripling the number of previously reportedrecords for this species. The results suggest that S. vespiformisis truly a rare species with a genuinely scattereddistribution, but can be locally abundant. Habitat analyseswere conducted in order to test the relationship betweenhabitat quality and the number of individuals caught. InSweden, S. vespiformis is thought to be associated with oakhosts, but our attempts to predict its occurrence by theabundance of oaks yielded no significant relationships. Wetherefore suggest that sampling bias and limited knowledgeon distribution may have led to the assumption that thisspecies is primarily reliant on oaks in the northern part ofits range, whereas it may in fact be polyphagous, similar toS. vespiformis found as an agricultural pest in Central andSouthern Europe. We conclude that pheromones canmassively enhance sampling potential for this and otherrare lepidopteran species. Large-scale pheromone-basedsurveys provide a snapshot of true presences and absencesacross a considerable part of a species national distributionrange, and thus for the first time provide a viable means ofsystematically assessing changes in distribution over timewith high spatiotemporal resolution.

  • 269.
    Bzhalava, David
    et al.
    Karolinska Institutet and Karolinska University Hospital, Stockholm.
    Ekström, Johanna
    Lund University, Malmö.
    Lysholm, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Hultin, Emilie
    Karolinska Institutet and Karolinska University Hospital, Stockholm.
    Faust, Helena
    Lund University, Malmö.
    Persson, Bengt
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Lehtinen, Matti
    National Institute for Health and Welfare, Oulu, Finland.
    de Villiers, Ethel-Michele
    Deutsches Krebsforschungszentrum, Heidelberg, Germany.
    Dillner, Joakim
    Karolinska Institutet and Karolinska University Hospital, Stockholm.
    Phylogenetically diverse TT virus viremia among pregnant women2012In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 432, no 2, p. 427-434Article in journal (Refereed)
    Abstract [en]

    Infections during pregnancy have been suggested to be involved in childhood leukemias. We used high-throughput sequencing to describe the viruses most readily detectable in serum samples of pregnantwomen. Serum DNA of 112 mothers to leukemic children was amplified using whole genome amplification. Sequencing identified one TTvirus (TTV) isolate belonging to a known type and two putatively new TTVs. For 22 mothers, we also performed TTV amplification by general primer PCR before sequencing. This detected 39 TTVs, two of which were identical to the TTVs found after whole genome amplification.

    Altogether, we found 40 TTV isolates, 29 of which were putatively new types (similarities ranging from 89% to 69%). In conclusion, high throughput sequencing is useful to describe the known or unknown viruses that are present in serum samples of pregnantwomen.

  • 270.
    Bäcklund, Fredrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Elfwing, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Ajjan, Fatimá Nadia
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Babenko, Viktoria
    Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Poland.
    Dzwolak, Wojciech
    Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Poland.
    Solin, Niclas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    PEDOT-S coated protein fibril microhelicesManuscript (preprint) (Other academic)
    Abstract [en]

    We show here the preparation and characterization of micrometer sized conductive helices. We utilize protein fibrils as structural templates to create chiral helices with either right or left handed helicity. The helices are coated with the conductive polymer alkoxysulfonate poly(ethylenedioxythiophene) (PEDOT-S) to create micrometer sized conductive helices. The coating acts as a stabilizer for the template structure, facilitates the preparation of solid state films and shows significant conductivity. The helices have been investigated using Circular Dichroism (CD) and scanning electron microscopy (SEM) and the conductivity have been measured for solid state films.

  • 271.
    Bäcklund, Fredrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Solin, Niclas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Development and Application of Methodology for Rapid Screening of Potential Amyloid Probes2014In: ACS COMBINATORIAL SCIENCE, ISSN 2156-8952, Vol. 16, no 12, p. 721-729Article in journal (Refereed)
    Abstract [en]

    Herein, we demonstrate that it is possible to rapidly screen hydrophobic fluorescent aromatic molecules with regards to their properties as amyloid probes. By grinding the hydrophobic molecule with the amyloidogenic protein insulin, we obtained a water-soluble composite material. When this material is dissolved and exposed to conditions promoting amyloid formation, the protein aggregates into amyloid fibrils incorporating the hydrophobic molecule. As a result, changes in the fluorescence spectra of the hydrophobic molecule can be correlated to the formation of amyloid fibrils, and the suitability of the hydrophobic molecular skeleton as an amyloid probe can thus be assessed. As a result, we discovered two new amyloid probes, of which one is the well-known laser dye DCM. The grinding method can also be used for rapid preparation of novel composite materials between dyes and proteins, which can be used in materials science applications such as organic electronics and photonics.

  • 272.
    Bäcklund, Fredrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Wigenius, Jens
    Chalmers, Sweden.
    Westerlund, Fredrik
    Chalmers, Sweden .
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Solin, Niclas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Amyloid fibrils as dispersing agents for oligothiophenes: control of photophysical properties through nanoscale templating and flow induced fibril alignment2014In: Journal of Materials Chemistry C, ISSN 2050-7526, E-ISSN 2050-7534, Vol. 2, no 37, p. 7811-7822Article in journal (Refereed)
    Abstract [en]

    Herein we report that protein fibrils formed from aggregated proteins, so called amyloid fibrils, serve as an excellent dispersing agent for hydrophobic oligothiophenes such as alpha-sexithiophene (6T). Furthermore, the protein fibrils are capable of orienting 6T along the fibril long axis, as demonstrated by flow-aligned linear dichroism spectroscopy and polarized fluorescence microscopy. The materials are prepared by solid state mixing of 6T with a protein capable of self-assembly. This results in a water soluble composite material that upon heating in aqueous acid undergoes self-assembly into protein fibrils non-covalently functionalized with 6T, with a typical diameter of 5-10 nm and lengths in the micrometre range. The resulting aqueous fibril dispersions are a readily available source of oligothiophenes that can be processed from aqueous solvent, and we demonstrate the fabrication of macroscopic structures consisting of aligned 6T functionalized protein fibrils. Due to the fibril induced ordering of 6T these structures exhibit polarized light emission.

  • 273.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Chicken domestication: Effects of tameness on brain gene expression and DNA methylation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Domestication greatly increases phenotypic variation in a short time span, with selection for a single phenotype and a plethora of associated phenotypic changes as an outcome of the process. The domestication process influences the underlying genomic architecture of a species, and the success and speed of the process is likely influenced by it. The main aims of my thesis was to study how domestication affects the brain of chickens: specifically changes in morphology, gene expression, and DNA methylation. Differences in gene expression and DNA methylation between White Leghorn and Red Junglefowl chickens were mapped, and inheritance of these patterns were quantified, indicating a faithful transmission of breed-specific epigenetic markers. Selection on the behavioral trait fearfulness, generated high and low fearful lines of Red Junglefowl. Both the parental population and the fifth selected generation were used for the analyses in this thesis. One experiment studied morphological changes in the brain and other vital organs, and found that relative total brain size increased in high fearful birds, as a consequence of an increase in cerebral hemisphere size in high fearful birds and not in low fearful birds. Also, the relative heart, liver, spleen and testis size increased in high fearful birds, indicating correlated morphological changes with selection for fearfulness. Two additional experiments examined differential gene expression in the hypothalamus and the anterior cerebral hemisphere. The hypothalamus differed in expression of genes with reproductive and immunological functions, whilst the cerebral hemisphere differed in expression of genes related to social behaviors and neurological functions especially those upregulated in low fearful birds.  These results indicate the occurrence of tissue- and species-specific changes in gene expression as overlap with other domestication events were nearly nonexistent. A fourth experiment sought to associate the change in fear levels and gene expression differences with DNA methylation. Chromosomal regions with differential DNA methylation between high and low fearful birds were identified, and genes in these regions had annotated functions relevant to phenotypic differences between the selection lines. This thesis is the first to study the genetic alterations of domestication using the wild ancestor of an already domesticated species to repeat the domestication process selecting against fear of humans. The findings corroborate results from previous comparisons of wild and domestic animals, and further support the theory that rigorous selection for a behavioral trait can cause a cascade of genetic and epigenetic changes facilitating the domestication of a population.

    List of papers
    1. Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens
    Open this publication in new window or tab >>Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens
    Show others...
    2012 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, no 59Article in journal (Refereed) Published
    Abstract [en]

    Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation. Here, we show that in Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differ substantially from that of a domesticated egg laying breed. Expression as well as methylation differences are largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences are tissue-specific, and the differential methylation at specific loci are little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication. Hence, our results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.

    Place, publisher, year, edition, pages
    BioMed Central, 2012
    Keywords
    Domestication, gene expression, tiling array, behaviour, methylation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-70159 (URN)10.1186/1471-2164-13-59 (DOI)000301440800001 ()
    Note

    funding agencies|Swedish Research Council| 2008-14496-59340-36 |Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning| 221 2007 838 |

    Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2019-03-05Bibliographically approved
    2. Domestication and tameness: brain geneexpression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology
    Open this publication in new window or tab >>Domestication and tameness: brain geneexpression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology
    Show others...
    2016 (English)In: Royal Society Open Science, E-ISSN 2054-5703, no 3, article id 160033Article in journal (Refereed) Published
    Abstract [en]

    The domestication of animals has generated a set of phenotypicmodifications, affecting behaviour, appearance, physiologyand reproduction, which are consistent across a range ofspecies. We hypothesized that some of these phenotypes couldhave evolved because of genetic correlation to tameness,an essential trait for successful domestication. Starting froman outbred population of red junglefowl, ancestor of alldomestic chickens, we selected birds for either high or lowfear of humans for five generations. Birds from the fifthselected generation (S5) showed a divergent pattern of growthand reproduction, where low fear chickens grew larger andproduced larger offspring. To examine underlying geneticmechanisms, we used microarrays to study gene expressionin thalamus/hypothalamus, a brain region involved in fearand stress, in both the parental generation and the S5. Whileparents of the selection lines did not show any differentiallyexpressed genes, there were a total of 33 genes with adjustedp-values below 0.1 in S5. These were mainly related to spermfunction,immunological functions, with only a few known tobe relevant to behaviour. Hence, five generations of divergentselection for fear of humans produced changes in hypothalamicgene expression profiles related to pathways associated withmale reproduction and to immunology. This may be linked to the effects seen on growth and size of offspring. These results support the hypothesis thatdomesticated phenotypes may evolve because of correlated effects related to reduced fear of humans.

    Place, publisher, year, edition, pages
    Royal Society Publishing, 2016
    Keywords
    artificial selection, gene expression, microarray, chicken, fearfulness
    National Category
    Ecology
    Identifiers
    urn:nbn:se:liu:diva-130501 (URN)10.1098/rsos.160033 (DOI)000384411000002 ()
    Note

    Funding agencies:  Research council Formas; Vetenskapsradet; ERC [322206]

    Available from: 2016-08-11 Created: 2016-08-11 Last updated: 2017-11-28
  • 274.
    Bélteky, Johan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Agnvall, Beatrix
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bektic, Lejla
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Höglund, Andrey
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Guerrero Bosagna, Carlos
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Epigenetics and early domestication: differences in hypothalamic DNA methylation between red junglefowl divergently selected for high or low fear of humans2018In: Genetics Selection Evolution, ISSN 0999-193X, E-ISSN 1297-9686, Vol. 50, article id 13Article in journal (Refereed)
    Abstract [en]

    Background: Domestication of animals leads to large phenotypic alterations within a short evolutionary time-period. Such alterations are caused by genomic variations, yet the prevalence of modified traits is higher than expected if they were caused only by classical genetics and mutations. Epigenetic mechanisms may also be important in driving domesticated phenotypes such as behavior traits. Gene expression can be modulated epigenetically by mechanisms such as DNA methylation, resulting in modifications that are not only variable and susceptible to environmental stimuli, but also sometimes transgenerationally stable. To study such mechanisms in early domestication, we used as model two selected lines of red junglefowl (ancestors of modern chickens) that were bred for either high or low fear of humans over five generations, and investigated differences in hypothalamic DNA methylation between the two populations. Results: Twenty-two 1-kb windows were differentially methylated between the two selected lines at p amp;lt; 0.05 after false discovery rate correction. The annotated functions of the genes within these windows indicated epigenetic regulation of metabolic and signaling pathways, which agrees with the changes in gene expression that were previously reported for the same tissue and animals. Conclusions: Our results show that selection for an important domestication-related behavioral trait such as tameness can cause divergent epigenetic patterns within only five generations, and that these changes could have an important role in chicken domestication.

  • 275.
    Bélteky, Johan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Agnvall, Beatrix
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Johnsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Domestication and tameness: brain geneexpression in red junglefowl selected for less fear of humans suggests effects on reproduction and immunology2016In: Royal Society Open Science, E-ISSN 2054-5703, no 3, article id 160033Article in journal (Refereed)
    Abstract [en]

    The domestication of animals has generated a set of phenotypicmodifications, affecting behaviour, appearance, physiologyand reproduction, which are consistent across a range ofspecies. We hypothesized that some of these phenotypes couldhave evolved because of genetic correlation to tameness,an essential trait for successful domestication. Starting froman outbred population of red junglefowl, ancestor of alldomestic chickens, we selected birds for either high or lowfear of humans for five generations. Birds from the fifthselected generation (S5) showed a divergent pattern of growthand reproduction, where low fear chickens grew larger andproduced larger offspring. To examine underlying geneticmechanisms, we used microarrays to study gene expressionin thalamus/hypothalamus, a brain region involved in fearand stress, in both the parental generation and the S5. Whileparents of the selection lines did not show any differentiallyexpressed genes, there were a total of 33 genes with adjustedp-values below 0.1 in S5. These were mainly related to spermfunction,immunological functions, with only a few known tobe relevant to behaviour. Hence, five generations of divergentselection for fear of humans produced changes in hypothalamicgene expression profiles related to pathways associated withmale reproduction and to immunology. This may be linked to the effects seen on growth and size of offspring. These results support the hypothesis thatdomesticated phenotypes may evolve because of correlated effects related to reduced fear of humans.

  • 276.
    Börjesson, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Antibiotic Resistance in Wastewater: Methicillin-resistant Staphylococcus aureus (MRSA)and antibiotic resistance genes2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A large part of the antibiotics consumed ends up in wastewater, and in the wastewater the antibiotics may exert selective pressure for or maintain resistance among microorganisms. Antibiotic resistant bacteria and genes encoding antibiotic resistance are commonly detected in wastewater, often at higher rates and concentrations compared to surface water. Wastewater can also provide favourable conditions for the growth of a diverse bacterial community, which constitutes a basis for the selection and spread of antibiotic resistance. Therefore, wastewater treatment plants have been suggested to play a role in the dissemination and development of antibiotic resistant bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is a large problem worldwide as a nosocomial pathogen, but knowledge is limited about occurrence in non-clinical environments, such as wastewater, and what role wastewater plays in dissemination and development of MRSA.

     

    In this thesis we investigated the occurrence of MRSA in a full-scale wastewater treatment plant (WWTP). We also investigated the concentration of genes encoding resistance to aminoglycosides (aac(6’)-Ie+aph(2’’)), β-lactam antibiotics (mecA) and tetracyclines (tetA and tetB) in three wastewater-associated environments: (1) soil from an overland flow area treating landfill leachates, (2) biofilm from a municipal wastewater treatment plant, and (3) sludge from a hospital wastewater pipeline. In addition, concentrations of mecA, tetA and tetB were investigated over the treatment process in the WWTP. These investigations were performed to determine how the prevalence and concentration of MRSA and the antibiotic resistence genes are affected in wastewater and wastewater treatment processes over time. The occurrence of MRSA was investigated by cultivation and a commercially available real-time PCR assay. In order to determine concentrations of the genes aac(6’)-Ie+aph(2’’), mecA, tetA and tetB in wastewater we developed a LUXTM real-time PCR assay for each gene.

     

    Using cultivation and real-time PCR we could for the first time describe the occurrence of MRSA in wastewater and show that it had a stable occurrence over time in a WWTP. MRSA could mainly be detected in the early treatment steps in the WWTP, and the wastewater treatment process reduced the number and diversity of cultivated MRSA. However, our results also indicate that the treatment process selects for strains with more extensive resistance and possibly higher virulence. The isolated wastewater MRSA strains were shown to have a close genetic relationship to clinical isolates, and no specific wastewater lineages could be detected, indicating that they are a reflection of carriage in the community. Taken together, these data indicate that wastewater may be a potential reservoir for MRSA and that MRSA are more prevalent in wastewater than was previously thought.

     

    The real-time PCR assays, for aac(6’)-Ie+aph(2’’), mecA, tetA, and tetB that we developed, were shown to be sensitive, fast, and reproducible methods for detection and quantification of these genes in wastewater environments. The highest concentrations of all genes were observed in the hospital pipeline, and the lowest in the overland flow system, with tetA and aac(6´)-Ie+aph(2´´) detected in all three environments. In the full-scale WWTP, we continuously detected mecA, tetA and tetB over the treatment process and over time. In addition, it was shown that the treatment process reduces concentrations of all three genes. The data presented in this thesis also indicate that the reduction for all three genes may be connected to the removal of biomass, and in the reduction of tetA and tetB, sedimentation and precipitation appear to play an important role.

    List of papers
    1. Quantification of genes encoding resistance to aminoglycosides, β-lactams and tetracyclines in wastewater environments by real-time PCR
    Open this publication in new window or tab >>Quantification of genes encoding resistance to aminoglycosides, β-lactams and tetracyclines in wastewater environments by real-time PCR
    Show others...
    2009 (English)In: International Journal of Environmental Health Research, ISSN 0960-3123, E-ISSN 1369-1619, p. 1-12Article in journal (Refereed) Published
    Abstract [en]

    In this study real-time PCR assays, based on the LUX-technique, were developed for quantification of genes mediating resistance to aminoglycosides [aac(6 ')-Ie + aph(2 ' ')], beta-lactams (mecA), and tetracyclines (tetA and tetB), for use in wastewater environments. The developed assays were applied on DNA extracted from three wastewater-associated environments: soil from an overland flow area treating landfill leachates, biofilm from a municipal wastewater treatment plant, and sludge from a hospital wastewater pipeline. The highest concentration of all genes was observed in the hospital pipeline and the lowest in the overland flow system. TetA and aac(6 ')-Ie + aph(2 ' ') could be detected in all environments. The tetB gene was detected in the overland flow area and the hospital wastewater pipeline and mecA was detected in the wastewater treatment plant and the hospital pipeline. The developed LUX real-time PCR assays were shown to be fast and reproducible tools for detection and quantification of the four genes encoding antibiotic resistance in wastewater.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2009
    Keywords
    Water pollutants; sewage pollution; water quality; aac(6')-Ie + aph(2''); mecA; tetA; tetB; LUX™ real-time PCR
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18293 (URN)10.1080/09603120802449593 (DOI)19370439 (PubMedID)
    Available from: 2009-05-15 Created: 2009-05-15 Last updated: 2017-12-13Bibliographically approved
    2. A seasonal study of the mecA gene and Staphylococcus aureus including methicillin-resistant S. aureus in a municipal wastewater treatment plant
    Open this publication in new window or tab >>A seasonal study of the mecA gene and Staphylococcus aureus including methicillin-resistant S. aureus in a municipal wastewater treatment plant
    2009 (English)In: Water Research, ISSN 0043-1354, E-ISSN 1879-2448, Vol. 43, no 4, p. 925-932Article in journal (Refereed) Published
    Abstract [en]

    The spread of methicillin-resistant Staphylococcus aureus (MRSA), in which the mecA gene mediates resistance, threatens the treatment of staphylococcal diseases. The aims were to determine the effect of wastewater treatment processes on mecA gene concentrations, and the prevalence of S. aureus and MRSA over time. To achieve this a municipal wastewater treatment plant was investigated for the mecA gene, S. aureus and MRSA, using real-time PCR assays. Water samples were collected monthly for one year, at eight sites in the plant, reflecting different aspects of the treatment process. The mecA gene and S. aureus could be detected throughout the year at all sampling sites. MRSA could also be detected, but mainly in the early treatment steps. The presence of MRSA was verified through cultivation from inlet water. The concentration of the mecA gene varied between months and sampling sites, but no obvious seasonal variation could be determined. The wastewater treatment process reduced the mecA gene concentration in most months. Taken together our results show that the mecA gene, S. aureus and MRSA occur over the year at all sites investigated.

    Keywords
    Methicillin-resistant, Staphylococcus aureus, mecA, LUX (TM) real-time PCR, spa Typing, Wastewater treatment plant, Seasonal study
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17599 (URN)10.1016/j.watres.2008.11.036 (DOI)19084256 (PubMedID)
    Note
    Original Publication: Stefan Börjesson, Sara Melin, Andreas Matussek and Per-Eric Lindgren, A seasonal study of the mecA gene and Staphylococcus aureus including methicillin-resistant S. aureus in a municipal wastewater treatment plant, 2009, Water Research, (43), 4, 925-932. http://dx.doi.org/10.1016/j.watres.2008.11.036 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2009-07-09 Created: 2009-04-06 Last updated: 2017-12-13Bibliographically approved
    3. Methicillin-resistant Staphylococcus aureus (MRSA) in municipal wastewater: An uncharted threat?
    Open this publication in new window or tab >>Methicillin-resistant Staphylococcus aureus (MRSA) in municipal wastewater: An uncharted threat?
    Show others...
    (English)Manuscript (Other academic)
    Abstract [en]

    Methicillin-resistant S. aureus (MRSA) was recently detected in municipal wastewater, why there is a need for further studies to elucidate if MRSA in wastewater constitutes a health risk, and to determine how wastewater treatment processes affects MRSA. We cultivated MRSA from a full-scale wastewater treatment plant to characterise the indigenous MRSA-flora and to investigate how the wastewater treatment process affects the clonal distribution. MRSA isolates were characterised using spa typing, antibiograms, SSCmec typing and detection of Panton Valentine leukocidin (PVL) genes. We found that the wastewater MRSA-flora has a close genetic relationship to clinical isolates, but we also isolated novel spa types, primarily from the activated sludge treatment step. The number of isolates and the diversity of MRSA are reduced by the treatment process, but the process also selects for more extensive antibiotic resistant strains as well as for PVL positive strains.

    Keywords
    Staphylococcus aureus, MRSA, methicillin, β-lactam, SCCmec, spa typing, Panton Valentine leukocidin, PVL, antibiotic resistance, antibiogram
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18295 (URN)
    Available from: 2009-05-15 Created: 2009-05-15 Last updated: 2010-01-14Bibliographically approved
    4. Genes encoding tetracycline resistance in a full-scale municipal wastewater treatment plant investigated during one year
    Open this publication in new window or tab >>Genes encoding tetracycline resistance in a full-scale municipal wastewater treatment plant investigated during one year
    (English)Manuscript (Other academic)
    Abstract [en]

    Tetracycline-resistant bacteria and genes encoding tetracycline resistance are common in anthropogenic environments. We studied how wastewater treatment affects the prevalence and concentration of two genes that encode resistance to tetracycline: tetA and tetB. Using real-time PCR we analysed wastewater samples collected monthly for one year at eight key-sites in a full-scale municipal wastewater treatment plant (WWTP). We detected tetA and tetB at each sampling site and the concentration of both genes, expressed per wastewater volume or per total-DNA, decreased over the treatment process. The reduction of tetA and tetB was partly the result of the sedimentation process. The ratio of tetA and tetB, respectively, to total DNA was lower in or after the biological processes. Taken together our data show that tetracycline resistance genes occur throughout the WWTP and that the concentrations are reduced under conventional operational strategies. However, it is not possible to conclude the eventual risk for humans with respect to resistance spreading.

    Keywords
    tetA, tetB, tetracycline, LUXTM real-time PCR, wastewater treatment plant
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18296 (URN)
    Available from: 2009-05-15 Created: 2009-05-15 Last updated: 2010-01-14Bibliographically approved
  • 277.
    Calais, Andreas
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Is personality dependent of growth rate in red junglefowl (Gallus gallus)?2013Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Personality has been reported in a large variety of animal species, but it is not obvious why animals have personality. Variation in physiological traits, such as growth rate, should theoretically affect variation in behaviours and thus can explain why we observe variation in personalities. Growth rate is, theoretically, positively correlated with active personality types. Empirical studies have reported this pattern in different fish species, but there are not yet many studies on endothermic animals. I have therefore scored behaviours of 100 red junglefowl (Gallus gallus) chicks in four personality assays; novel arena, novel object, tonic immobility, and a proactive-reactive test, together with recording variation in growth rate of these individuals. The chicks individual growth rate (% day-1) were calculated and the relationship between personality and growth rate investigated. There was significant difference in growth rate between the sexes, where males grew faster than females, detected already at one week of age. However, no significant correlations between behavioural traits and growth rate were observed, indicating that personality seem to be independent of growth rate. Further studies should therefore investigate the generality of this finding, and alternative underlying mechanisms for variation in personality should be explored.

  • 278.
    Calais, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Poor welfare or future investment? Different growth pattern of broiler breeders2015Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    The parental stock of meat type chickens (broiler breeders) are commonly feed restricted to decrease their rapid growth and the issues associated with it. Among these birds, chronic hunger and stress are the most prominent welfare concerns and mass heterogeneity within flocks a major management challenge. The present study compared small and large broiler breeders of the same age within a flock, with the hypothesis that small birds would show signs of poorer welfare indicated by higher corticosterone concentration and heterophil/lymphocyte ratio as a consequence of higher experienced feed restriction due to competition. It also aimed to characterize morphometric differences between small and large birds within flocks as well as between birds on different feeding regimens; skip-a-day vs. every-day-fed. Heterophil/lymphocyte ratio at 4 weeks was significantly higher in large birds compared to small birds, but corticosterone concentration did not differ. Relative mass of the upper gastrointestinal tract, pancreas and liver of small birds at 4 weeks of age were significantly larger, while relative muscle and gizzard fat mass were significantly lower compared to large birds. 12 weeks old skip-a-day fed birds largely followed the pattern of 4 weeks old small birds. In the present study, no clear signs of poorer welfare in small broiler breeders could be seen and the morphometric differences might suggest different ways to cope with feed competition. A larger gastrointestinal tract might indicate long-term investments and maybe that smaller broiler breeders, and skip-a-day fed birds, are better habituated to feed restriction.

  • 279.
    Camacho, Rafael
    et al.
    Lund University, Sweden.
    Meyer, Matthias
    Lund University, Sweden.
    Vandewal, Koen
    Technical University of Dresden, Germany.
    Tang, Zheng
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Scheblykin, Ivan G.
    Lund University, Sweden.
    Polarization Imaging of Emissive Charge Transfer States in Polymer/Fullerene Blends2014In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 26, no 23, p. 6695-6704Article in journal (Refereed)
    Abstract [en]

    Photoexcitation of conjugated polymerfullerene blends results in population of a local charge transfer (CT) state at the interface between the two materials. The competition between recombination and dissociation of this interfacial state limits the generation of fully separated free charges. Therefore, a detailed understanding of the CT states is critical for building a comprehensive picture of the organic solar cells operation. We applied a new fluorescence microscopy method called two-dimensional polarization imaging to gain insight into the orientation of the transition dipole moments of the CT states, and the associated excitation energy transfer processes in TQ1:PCBM blend films. The polymer phase was oriented mechanically to relate the polymer dipole moment orientation to that of the CT states. CT state formation was observed to be much faster than energy transfer in the polymer phase. However, after being formed an emissive CT state does not exchange excitation energy with other CT states, suggesting that they are spatially and/or energetically isolated. We found that the quantum yield of the CT emission is smaller for CT states spatially located in the highly oriented polymer domains, which is interpreted as the result of enhanced CT state dissociation in highly ordered structures.

  • 280.
    Campos, Alexandre
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Danielsson, Gabriela
    Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
    Farinha, Ana Paula
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kuruvilla, Jacob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Warholm, Per
    Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University.
    Shotgun proteomics to unravel marine mussel (Mytilus edulis) response to long-term exposure to low salinity and propranolol in a Baltic Sea microcosm2016In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 137, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Pharmaceuticals, among them the β-adrenoreceptor blocker propranolol, are an important group of environmental contaminants reported in European waters. Laboratory exposure to pharmaceuticals on marine species has been performed without considering the input of the ecosystem flow. To unravel the ecosystem response to long-term exposure to propranolol we have performed long-term exposure to propranolol and low salinity in microcosms. We applied shotgun proteomic analysis to gills of Mytilus edulis from those Baltic Sea microcosms and identified 2071 proteins with a proteogenomic strategy. The proteome profiling patterns from the 587 highly reproductive proteins among groups define salinity as a key factor in the mussel´s response to propranolol. Exposure at low salinity drives molecular mechanisms of adaptation based on a decrease in the abundance of several cytoskeletal proteins, signalling and intracellular membrane trafficking pathway combined with a response towards the maintenance of transcription and translation. The exposure to propranolol combined with low salinity modulates the expression of structural proteins including cilia functions and decrease the expression membrane protein transporters. This study reinforces the environment concerns of the impact of low salinity in combination with anthropogenic pollutants and anticipate critical physiological conditions for the survival of the blue mussel in the northern areas.

  • 281.
    Campoy-Quiles, M.
    et al.
    ICMAB CSIC, Spain.
    Müller, Christian
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology. ICMAB CSIC, Spain.
    Garriga, M.
    ICMAB CSIC, Spain.
    Wang, E.
    Chalmers, Sweden.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Alonso, M. I.
    ICMAB CSIC, Spain.
    On the complex refractive index of polymer:fullerene photovoltaic blends2014In: Thin Solid Films, ISSN 0040-6090, E-ISSN 1879-2731, Vol. 571, p. 371-376Article in journal (Refereed)
    Abstract [en]

    We present a detailed investigation of the refractive index of polymer:fullerene blends for photovoltaic applications. The donor polymers poly[2,7-(9,9-dioctylfluorene)-alt-5,5-(4,7-di-2-thienyl-2,1,3-benzothiadiazole)] (APFO3), poly[2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt-thiophene-2,5-diyl] (TQ1), and poly[2,7-(9,9-dioctylfluorene)-alt-5,5-(5,10-di-2-thienyl-2,3,7,8-tetraphenyl-pyrazino[2,3-g] quinoxaline)] (APFO-Green9) were blended with either [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM) or [6,6]-phenyl-C-71-butyric acid methyl ester (PC71BM). We measured variable angle spectroscopic ellipsometry for three systems, namely APFO3:PCBM, TQ1:PC71BM and APFO-Green9:PC71BM, as a function of composition and analyze the data employing a number of models. We found that Bruggeman effective medium approximations (EMA) are not precise for the description of the optical properties of these blends. This is due to a number of reasons. First, we find that there are energy shifts associated to changes in conjugation length that cannot be accounted for using EMA. Second, blending results in a strong reduction of anisotropy. Finally, our data suggest that there is some degree of vertical segregation between components. Therefore, our results support the idea that the optical properties of polymer:fullerene mixtures should be treated as alloys rather than non-interacting blends.

  • 282.
    Cantù, Claudio
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Zurich, Switzerland.
    Felker, Anastasia
    Univ Zurich, Switzerland.
    Zimmerli, Dario
    Univ Zurich, Switzerland.
    Prummel, Karin D.
    Univ Zurich, Switzerland.
    Cabello, Elena M.
    Univ Zurich, Switzerland.
    Chiavacci, Elena
    Univ Zurich, Switzerland; Int Ctr Genet Engn and Biotechnol ICGEB Trieste, Italy.
    Mendez-Acevedo, Kevin M.
    Max Delbruck Ctr Mol Med, Germany.
    Kirchgeorg, Lucia
    Univ Zurich, Switzerland.
    Burger, Sibylle
    Univ Zurich, Switzerland.
    Ripoll, Jorge
    Univ Carlos III Madrid, Spain.
    Valenta, Tomas
    Univ Zurich, Switzerland.
    Hausmann, George
    Univ Zurich, Switzerland.
    Vilain, Nathalie
    Ecole Polytech Fed Lausanne, Switzerland.
    Aguet, Michel
    Ecole Polytech Fed Lausanne, Switzerland.
    Burger, Alexa
    Univ Zurich, Switzerland.
    Panakova, Daniela
    Max Delbruck Ctr Mol Med, Germany; Deutsch Zentrum Herz Kreislauf Forsch DZHK, Germany.
    Basler, Konrad
    Univ Zurich, Switzerland.
    Mosimann, Christian
    Univ Zurich, Switzerland.
    Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/beta-catenin signaling2018In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 32, no 21-22, p. 1443-1458Article in journal (Refereed)
    Abstract [en]

    Bcl9 and Pygopus (Pygo) are obligate Wnt/beta-catenin cofactors in Drosophila, yet their contribution to Wnt signaling during vertebrate development remains unresolved. Combining zebrafish and mouse genetics, we document a conserved, beta-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development. Disrupting the beta-catenin-BCL9-Pygo complex results in a broadly maintained canonical Wnt response yet perturbs heart development and proper expression of key cardiac regulators. Our work highlights BCL9 and Pygo as selective beta-catenin cofactors in a subset of canonical Wnt responses during vertebrate development. Moreover, our results implicate alterations in BCL9 and BCL9L in human congenital heart defects.

  • 283.
    Cantù, Claudio
    et al.
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Grande, Vito
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Alborelli, Ilaria
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Cassinelli, Letizia
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Cantù, Ileana
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Colzani, Maria Teresa
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Ierardi, Rossella
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy.
    Ronzoni, Luisa
    Dipartimento di Medicina Interna, Università di Milano, Fondazione Policlinico Mangiagalli, Regina Elena, IRCCS, Milano, Italy.
    Cappellini, Maria Domenica
    Dipartimento di Medicina Interna, Università di Milano, Fondazione Policlinico Mangiagalli, Regina Elena, IRCCS, Milano, Italy.
    Ferrari, Giuliana
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, 20132 Milan // Vita-Salute San Raffaele University, Milan, Italy.
    Ottolenghi, Sergio
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    Ronchi, Antonella
    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
    A highly conserved SOX6 double binding site mediates SOX6 gene downregulation in erythroid cells2011In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 39, no 2, p. 486-501Article in journal (Refereed)
    Abstract [en]

    The Sox6 transcription factor plays critical roles in various cell types, including erythroid cells. Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes. To identify new Sox6 target genes in erythroid cells, we used the known repressive double Sox6 consensus within the εy-globin promoter to perform a bioinformatic genome-wide search for similar, evolutionarily conserved motifs located within genes whose expression changes during erythropoiesis. We found a highly conserved Sox6 consensus within the Sox6 human gene promoter itself. This sequence is bound by Sox6 in vitro and in vivo, and mediates transcriptional repression in transient transfections in human erythroleukemic K562 cells and in primary erythroblasts. The binding of a lentiviral transduced Sox6FLAG protein to the endogenous Sox6 promoter is accompanied, in erythroid cells, by strong downregulation of the endogenous Sox6 transcript and by decreased in vivo chromatin accessibility of this region to the PstI restriction enzyme. These observations suggest that the negative Sox6 autoregulation, mediated by the double Sox6 binding site within its own promoter, may be relevant to control the Sox6 transcriptional downregulation that we observe in human erythroid cultures and in mouse bone marrow cells in late erythroid maturation.

  • 284.
    Cantù, Claudio
    et al.
    Institute of Molecular Life Sciences, University of Zurich, Switzerland.
    Valenta, Tomas
    Institute of Molecular Life Sciences, University of Zurich, Switzerland.
    Basler, Konrad
    Institute of Molecular Life Sciences, University of Zurich, Switzerland.
    A RING finger to wed TCF and β-catenin2013In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 14, no 4, p. 295-296Article in journal (Refereed)
  • 285.
    Cao, Z.
    et al.
    Department of Chemical Science and Technologies, University of Tor Vergata, Rome, Italy, Department of Chemistry and Molecular Engineering, East China University of of Science and Technology, Shanghai, China.
    Lvova, L.
    Department of Chemical Science and Technologies, University of Tor Vergata, Rome, Italy, Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg, Russia.
    Paolesse, R.
    Department of Chemical Science and Technologies, University of Tor Vergata, Rome, Italy.
    Di Natale, C
    Department of Electronic Engineering, University of Tor Vergata, Rome, Italy.
    D' Amico, A.
    Department of Electronic Engineering, University of Tor Vergata, Rome, Italy.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Porphyrin electropolymers as opto-electrochemical probe for the detection of red-ox analytes2014In: Sensors: Proceedings of the First National Conference on Sensors, Rome 15-17 February, 2012, Springer Science Business Media , 2014, Vol. 162 LNEE, p. 49-55Conference paper (Refereed)
    Abstract [en]

    The application of pyrrole-substituted porphyrin electropolymers for simultaneous optical and electrochemical analysis of red-ox active analytes, namely diazo-conjugated dyes of Sudan family, is presented. Sudan colorants are widely used in many fields, but accurate screening of their consumption is required due to their high toxicity. The inherent electrochemical activity of Sudan dyes, as far as their intense coloration, makes possible to find the appropriate conditions of hybrid optical and electrochemical porphyrin electropolymer based sensor array system application. This approach allowed a significant increase in the chemical information, improving the analytical system performance in terms of selectivity and sensitivity, and permitted the fast and simple monitoring of Sudan dye analytes.

  • 286.
    Cardemil, Carina
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
    Effects of antiresorptive agents on inflammation and bone regeneration in different osseous sites - experimental and clinical studies2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The biological mechanisms involved in bone regeneration in osteoporotic bone and the effect of antiresorptive drugs in relation to surgically inserted biomaterials are not fully understood. Improved osseointegration of titanium implants but also adverse effects of antiresorptive therapies, such as osteonecrotic jaw have been described in the literature. The aims of this research project were, firstly, to investigate and to understand the biological events determining bone regeneration and implant integration, after administration of antiresorptive agents; secondly, to determine the cellular and molecular patterns of bone regeneration at implants and synthetic bone substitutes under osteoporotic conditions and, thirdly, to determine how different skeletal sites are affected. The present research included a study of jawbone morphology and gene expression in patients treated with systemic bisphosphonates. When compared to controls, higher gene expression levels of IL-1β was observed in bisphosphonate treated patients with osteonecrosis while bisphosphonate treated patients without necrosis showed lower expression levels of caspase 8, an apoptosis marker involved in the immune response. In ovariectomised rats, zoledronic acid resulted in site-specific differences in the rate of osseointegration and also of gene expression involved in bone healing and regeneration. Strontium-doped calcium phosphate inserted in the rat femur induced lower expression of osteoclastic markers compared to hydroxyapatite and higher bone formation in the periphery of the defects. Whereas major structural changes were demonstrated in the long bones of the ovariectomised rat, less structural alterations were shown in the mandible. However, ovariectomy resulted in lower expression of genes coding for bone formation and angiogenesis in the mandible. In conclusion, the present study shows that the mandible is differently affected by experimentally induced estrogen deficiency than the long bones. Bisphosphonates, administered systemically to estrogen deficient animals, impair osseointegration in the mandible, at least partly related to a downregulation of genes important for the osteogenic process. These observations may have implications for understanding the mechanisms involved in the deranged bone healing observed in the jawbone of bisphosphonate treated patients.

    List of papers
    1. The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.
    Open this publication in new window or tab >>The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.
    Show others...
    2013 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, no 5, p. 1546-1561Article in journal (Refereed) Published
    Abstract [en]

    Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28 d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.

    National Category
    Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-135755 (URN)10.1016/j.biomaterials.2012.11.003 (DOI)23182921 (PubMedID)
    Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2018-01-13
    2. Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats
    Open this publication in new window or tab >>Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats
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    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84932Article in journal (Refereed) Published
    Abstract [en]

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

    National Category
    Biomaterials Science Medical Materials Medical Biotechnology Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-136113 (URN)10.1371/journal.pone.0084932 (DOI)24376855 (PubMedID)
    Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-01-13Bibliographically approved
  • 287.
    Cardoso-Moreira, Margarida
    et al.
    Heidelberg Univ ZMBH, Germany; Univ Lausanne, Switzerland.
    Halbert, Jean
    Univ Lausanne, Switzerland.
    Valloton, Delphine
    Univ Lausanne, Switzerland.
    Velten, Britta
    European Mol Biol Lab, Germany.
    Chen, Chunyan
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Shao, Yi
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Liechti, Angelica
    Univ Lausanne, Switzerland.
    Ascencao, Kelly
    Univ Lausanne, Switzerland.
    Rummel, Coralie
    Univ Lausanne, Switzerland.
    Ovchinnikova, Svetlana
    Heidelberg Univ ZMBH, Germany.
    Mazin, Pavel V.
    Skolkovo Inst Sci and Technol, Russia; RAS, Russia; HSE Univ, Russia.
    Xenarios, Ioannis
    Univ Lausanne, Switzerland.
    Harshman, Keith
    Univ Lausanne, Switzerland.
    Mort, Matthew
    Cardiff Univ, Wales.
    Cooper, David N.
    Cardiff Univ, Wales.
    Sandi, Carmen
    Ecole Polytech Fed Lausanne, Switzerland.
    Soares, Michael J.
    Univ Kansas, MO USA; Childrens Mercy, MO USA.
    Ferreira, Paula G.
    Univ Porto, Portugal; Univ Porto, Portugal.
    Afonso, Sandra
    Univ Porto, Portugal.
    Carneiro, Miguel
    Univ Porto, Portugal; Univ Porto, Portugal.
    Turner, James M. A.
    Francis Crick Inst, England.
    VandeBerg, John L.
    Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA; Univ Texas Rio Grande Valley, TX USA.
    Fallahshahroudi, Amir
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Behr, Ruediger
    Leibniz Inst Primate Res DPZ, Germany; DZHK German Ctr Cardiovasc Res, Germany.
    Lisgo, Steven
    Newcastle Univ, England.
    Lindsay, Susan
    Newcastle Univ, England.
    Khaitovich, Philipp
    Skolkovo Inst Sci and Technol, Russia; Chinese Acad Sci, Peoples R China; Univ Chinese Acad Sci, Peoples R China.
    Huber, Wolfgang
    European Mol Biol Lab, Germany.
    Baker, Julie
    Stanford Univ, CA 94305 USA.
    Anders, Simon
    Heidelberg Univ ZMBH, Germany.
    Zhang, Yong E.
    Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China; Chinese Acad Sci, Peoples R China.
    Kaessmann, Henrik
    Heidelberg Univ ZMBH, Germany.
    Gene expression across mammalian organ development2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 571, no 7766, p. 505-+Article in journal (Refereed)
    Abstract [en]

    The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.

  • 288.
    Caren, Helena
    et al.
    University of Gothenburg, Sweden.
    Erichsen, Jennie
    University of Gothenburg, Sweden.
    Olsson, Linda
    University of Gothenburg, Sweden.
    Enerbäck, Charlotta
    University of Gothenburg, Sweden.
    Sjoberg, Rose-Marie
    University of Gothenburg, Sweden.
    Abrahamsson, Jonas
    University of Gothenburg, Sweden.
    Kogner, Per
    Childhood Canc Res Unit, SE-17176 Stockholm, Sweden .
    Martinsson, Tommy
    University of Gothenburg, Sweden.
    High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: Four cases of homozygous deletions of the CDKN2A gene2008In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 9, no 353Article in journal (Refereed)
    Abstract [en]

    Background: Neuroblastoma is a very heterogeneous pediatric tumor of the sympathetic nervous system showing clinically significant patterns of genetic alterations. Favorable tumors usually have near-triploid karyotypes with few structural rearrangements. Aggressive stage 4 tumors often have near-diploid or near-tetraploid karyotypes and structural rearrangements. Whole genome approaches for analysis of genome-wide copy number have been used to analyze chromosomal abnormalities in tumor samples. We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP) arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets. Results: Ninety-two neuroblastoma tumors were analyzed with 50 K and/or 250 K SNP arrays from Affymetrix, using CNAG3.0 software. Thirty percent of the tumors harbored 1p deletion, 22% deletion of 11q, 26% had MYCN amplification and 45% 17q gain. Most of the tumors with 1p deletion were found among those with MYCN amplification. Loss of 11q was most commonly seen in tumors without MYCN amplification. In the case of MYCN amplification, two types were identified. One type displayed simple continuous amplicons; the other type harbored more complex rearrangements. MYCN was the only common gene in all cases with amplification. Complex amplification on chromosome 12 was detected in two tumors and three different overlapping regions of amplification were identified. Two regions with homozygous deletions, four cases with CDKN2A deletions in 9p and one case with deletion on 3p (the gene RBMS3) were also detected in the tumors. Conclusion: SNP arrays provide useful tools for high-resolution characterization of significant chromosomal rearrangements in neuroblastoma tumors. The mapping arrays from Affymetrix provide both copy number and allele-specific information at a resolution of 10-12 kb. Chromosome 9p, especially the gene CDKN2A, is subject to homozygous (four cases) and heterozygous deletions (five cases) in neuroblastoma tumors.

  • 289.
    Carlen, Ida
    et al.
    AquaBiota Water Res, Sweden; Stockholm Univ, Sweden.
    Thomas, Len
    Univ St Andrews, Scotland.
    Carlstrom, Julia
    AquaBiota Water Res, Sweden; Swedish Museum Nat Hist, Sweden.
    Amundin, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Kolmarden Wildlife Pk, Sweden.
    Teilmann, Jonas
    Aarhus Univ, Denmark.
    Tregenza, Nick
    Chelonia Ltd, England.
    Tougaard, Jakob
    Aarhus Univ, Denmark.
    Koblitz, Jens C.
    German Oceanog Museum, Germany; Max Planck Inst Ornithol, Germany; Univ Constance, Germany.
    Sveegaard, Signe
    Aarhus Univ, Denmark.
    Wennerberg, Daniel
    Kolmarden Wildlife Pk, Sweden.
    Loisa, Olli
    Turku Univ Appl Sci, Finland.
    Daehne, Michael
    German Oceanog Museum, Germany.
    Brundiers, Katharina
    German Oceanog Museum, Germany.
    Kosecka, Monika
    Univ Gdansk, Poland; Tech Univ Catalonia, Spain.
    Kyhn, Line Anker
    Aarhus Univ, Denmark.
    Ljungqvist, Cinthia Tiberi
    Calluna AB, SE-58228 Linkoping, Sweden.
    Pawliczka, Iwona
    Univ Gdansk, Poland.
    Koza, Radomil
    Univ Gdansk, Poland.
    Arciszewski, Bartlomiej
    Univ Gdansk, Poland.
    Galatius, Anders
    Aarhus Univ, Denmark.
    Jabbusch, Martin
    German Oceanog Museum, Germany.
    Laaksonlaita, Jussi
    Turku Univ Appl Sci, Finland.
    Niemi, Jussi
    Turku Univ Appl Sci, Finland.
    Lyytinen, Sami
    Turku Univ Appl Sci, Finland.
    Gallus, Anja
    German Oceanog Museum, Germany.
    Benke, Harald
    German Oceanog Museum, Germany.
    Blankett, Penina
    Minist Environm, Finland.
    Skora, Krzysztof E.
    Univ Gdansk, Poland.
    Acevedo-Gutierrez, Alejandro
    Western Washington Univ, WA 98225 USA.
    Basin-scale distribution of harbour porpoises in the Baltic Sea provides basis for effective conservation actions2018In: Biological Conservation, ISSN 0006-3207, E-ISSN 1873-2917, Vol. 226, p. 42-53Article in journal (Refereed)
    Abstract [en]

    Knowledge on spatial and seasonal distribution of species is crucial when designing protected areas and implementing management actions. The Baltic Proper harbour porpoise (Phocoena phocoena) population is critically endangered, and its distribution is virtually unknown. Here, we used passive acoustic monitoring and species distribution models to describe the spatial and seasonal distribution of harbour porpoises in the Baltic Proper. Porpoise click detectors were deployed over a systematic grid of 297 stations in eight countries from April 2011 through July 2013. Generalized additive models were used to describe the monthly probability of detecting porpoise clicks as a function of spatially-referenced covariates and time. During the reproductive season, two main areas of high probability of porpoise detection were identified. One of those areas, situated on and around the offshore banks in the Baltic Proper, is clearly separated from the known distribution range of the Belt Sea population during breeding season, suggesting this is an important breeding ground for the Baltic Proper population. We commend the designation of this area as a marine protected area and recommend Baltic Sea countries to also protect areas in the southern Baltic Sea and the Hand Bight where additional important harbour porpoise habitats were identified. Further conservation measures should be carried out based on analyses of overlap between harbour porpoise distribution and potentially harmful anthropogenic activities. Our study shows that large-scale systematic monitoring using novel techniques can give important insights on the distribution of low-density populations, and that international cooperation is pivotal when studying transnationally migratory species.

  • 290.
    Carlsson, Evelina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Danielsson, Elsa
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Det svenska skogsbrukets påverkan på den biologiska mångfalden: och ett förslag på hur lärare kan undervisa om detta i gymnasieskolan2016Student paper other, 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med denna litteraturstudie är att ge en bild av det svenska skogsbruket och dess påverkan på den biologiska mångfalden. Idag är det trakthyggesbruket som mest påverkar den biologiska mångfalden i Sverige och har lett till att många skogslevande arter idag är hotade och rödlistade. I denna studie har vi tittat på hur en produktionsskog skiljer sig från en naturskog när det gäller trädsammansättning, förekomst av död ved, fragmentering, skogskontinuitet och störning i form av brand. Vi har tittat på hur organismgrupperna svampar, lavar, mossor, kärlväxter, insekter, fåglar och däggdjur påverkas av skogsbruket. I denna studie ger vi även ett förslag på hur lärare, genom en exkursion, kan lära ut om biologisk mångfald i skolan. 

  • 291.
    Carlsson, Evelina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology.
    Danielsson, Elsa
    Linköping University, Department of Physics, Chemistry and Biology.
    En jämförande studie av skogsstrukturer i olika skogstyper i Östergötland: och ett förslag på hur ett biologiprojekt som behandlar detta kan genomföras i gymnasiekursen Biologi 12017Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med denna studie är att undersöka vilka skillnader i skogsstrukturer det finns mellan olika skogstyper i Östergötland, samt att diskutera hur dessa skillnader kan påverka den biologiska mångfalden. De skogstyper vi besökt är; hyggen, skogar som är ungefär 40 år gamla, avverkningsanmälda skogar samt naturskogar som är bevarade som naturreservat. De skogsstrukturer vi undersökt är; trädarter, diameter på träd och död ved, nedbrytningsstadie på död ved, spår av brand samt antal håligheter i träd och död ved. Vår studie visade att alla skogstyper hade åtminstone någon av de strukturer som kännetecknar en skog med höga naturvärden och därmed högre biologisk mångfald.  Naturreservat var den skogstyp som hade flest skogsstrukturer som kännetecknar skogar med höga naturvärden. Detta tyder på att de hade en större biologisk mångfald gentemot de andra skogstyperna. Hyggen var den skogstyp som uppvisade minst skogsstrukturer som kännetecknar skogar med höga naturvärden vilket tyder på att den biologiska mångfalden var minst på hyggen. Syftet med studien är även att utforma en skoluppgift som liknar vår studie men är anpassad till biologiundervisningen i gymnasieskolan. För att göra detta har vi valt att återskapa vårt arbete som ett biologiprojekt för gymnasiekursen Biologi 1. Detta biologiprojekt innefattar en exkursion med förberedelser och efterarbete. 

  • 292.
    Carlsson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics . Linköping University, The Institute of Technology.
    Mutational effects on protein structure and function2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis several important proteins are investigated from a structural perspective. Some of the proteins are disease related while other have important but not completely characterised functions. The techniques used are general as demonstrated by applications on metabolic proteins (CYP21, CYP11B1, IAPP, ADH3), regulatory proteins (p53, GDNF) and a transporter protein (ANTR1).

    When the protein CYP21 (steroid 21-hydroxylase) is deficient it causes CAH (congenital adrenal hyperplasia). For this protein, there are about 60 known mutations with characterised clinical phenotypes. Using manual structural analysis we managed to explain the severity of all but one of the mutations. By observing the properties of these mutations we could perform good predictions on, at the time, not classified mutations.

    For the cancer suppressor protein p53, there are over thousand mutations with known activity. To be able to analyse such a large number of mutations we developed an automated method for evaluation of the mutation effect called PREDMUT. In this method we include twelve different prediction parameters including two energy parameters calculated using an energy minimization procedure. The method manages to differentiate severe mutations from non-severe mutations with 77% accuracy on all possible single base substitutions and with 88% on mutations found in breast cancer patients.

    The automated prediction was further applied to CYP11B1 (steroid 11-beta-hydroxylase), which in a similar way as CYP21 causes CAH when deficient. A generalized method applicable to any kind of globular protein was developed. The method was subsequently evaluated on nine additional proteins for which mutants were known with annotated disease phenotypes. This prediction achieved 84% accuracy on CYP11B1 and 81% accuracy in total on the evaluation proteins while leaving 8% as unclassified. By increasing the number of unclassified mutations the accuracy of the remaining mutations could be increased on the evaluation proteins and substantially increase the classification quality as measured by the Matthews correlation coefficient. Servers with predictions for all possible single based substitutions are provided for p53, CYP21 and CYP11B1.

    The amyloid formation of IAPP (islet amyloid polypeptide) is strongly connected to diabetes and has been studied using both molecular dynamics and Monte Carlo energy minimization. The effects of mutations on the amount and speed of amyloid formation were investigated using three approaches. Applying a consensus of the three methods on a number of interesting mutations, 94% of the mutations could be correctly classified as amyloid forming or not, evaluated with in vitro measurements.

    In the brain there are many proteins whose functions and interactions are largely unknown. GDNF (glial cell line-derived neurotrophic factor) and NCAM (neural cell adhesion molecule) are two such neuron connected proteins that are known to interact. The form of interaction was studied using protein--protein docking where a docking interface was found mediated by four oppositely charged residues in respective protein. This interface was subsequently confirmed by mutagenesis experiments. The NCAM dimer interface upon binding to the GDNF dimer was also mapped as well as an additional interacting protein, GFRα1, which was successfully added to the protein complex without any clashes.

    A large and well studied protein family is the alcohol dehydrogenase family, ADH. A class of this family is ADH3 (alcohol dehydrogenase class III) that has several known substrates and inhibitors. By using virtual screening we tried to characterize new ligands. As some ligands were already known we could incorporate this knowledge when the compound docking simulations were scored and thereby find two new substrates and two new inhibitors which were subsequently successfully tested in vitro.

    ANTR1 (anion transporter 1) is a membrane bound transporter important in the photosynthesis in plants. To be able to study the amino acid residues involved in inorganic phosphate transportation a homology model of the protein was created. Important residues were then mapped onto the structure using conservation analysis and we were in this way able to propose roles of amino acid residues involved in the transportation of inorganic phosphate. Key residues were subsequently mutated in vitro and a transportation process could be postulated.

    To conclude, we have used several molecular modelling techniques to find functional clues, interaction sites and new ligands. Furthermore, we have investigated the effect of muations on the function and structure of a multitude of disease related proteins.

     

    List of papers
    1. Molecular Model of Human CYP21 Based onMammalian CYP2C5: Structural Features Correlatewith Clinical Severity of Mutations CausingCongenital Adrenal Hyperplasia
    Open this publication in new window or tab >>Molecular Model of Human CYP21 Based onMammalian CYP2C5: Structural Features Correlatewith Clinical Severity of Mutations CausingCongenital Adrenal Hyperplasia
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    2006 (English)In: Molecular Endocrinology, ISSN 0888-8809, E-ISSN 1944-9917, Vol. 20, no 11, p. 2946-2964Article in journal (Refereed) Published
    Abstract [en]

    Enhanced understanding of structure-function relationshipsof human 21-hydroxylase, CYP21, is requiredto better understand the molecular causesof congenital adrenal hyperplasia. To this end, astructural model of human CYP21 was calculatedbased on the crystal structure of rabbit CYP2C5.All but two known allelic variants of missense type,a total of 60 disease-causing mutations and sixnormal variants, were analyzed using this model. Astructural explanation for the corresponding phenotypewas found for all but two mutants for whichavailable clinical data are also discrepant with invitro enzyme activity. Calculations of protein stabilityof modeled mutants were found to correlateinversely with the corresponding clinical severity.Putative structurally important residues were identifiedto be involved in heme and substrate binding,redox partner interaction, and enzyme catalysisusing docking calculations and analysis of structurallydetermined homologous cytochrome P450s(CYPs). Functional and structural consequences ofseven novel mutations, V139E, C147R, R233G,T295N, L308F, R366C, and M473I, detected inScandinavian patients with suspected congenitaladrenal hyperplasia of different severity, were predictedusing molecular modeling. Structural featuresdeduced from the models are in good correlationwith clinical severity of CYP21 mutants,which shows the applicability of a modeling approachin assessment of new CYP21 mutations.

    Place, publisher, year, edition, pages
    Stanford: The endocrin society, 2006
    Keywords
    Mutations, prediction, CAH, CYP21, homology model
    National Category
    Bioinformatics and Systems Biology
    Identifiers
    urn:nbn:se:liu:diva-21305 (URN)10.1210/me.2006-0172 (DOI)
    Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2017-12-13Bibliographically approved
    2. Investigation and prediction of the severity of p53 mutants using parameters from structural calculations
    Open this publication in new window or tab >>Investigation and prediction of the severity of p53 mutants using parameters from structural calculations
    2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 15, p. 4142-4155Article in journal (Refereed) Published
    Abstract [en]

    A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important parameter is the stability measure of the mutated structure calculated using molecular modelling. For each mutant, a severity score is reported, which can be used for classification into deleterious and nondeleterious. Both structural features and sequence properties are taken into account. The method has a prediction accuracy of 77% on all mutants and 88% on breast cancer mutations affecting WAF1 promoter binding. When compared with earlier methods, using the same dataset, our method clearly performs better. As a result of the severity score calculated for every mutant, valuable knowledge can be gained regarding p53, a protein that is believed to be involved in over 50% of all human cancers.

    Keywords
    Cancer; molecular modelling; mutations; p53; structural prediction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20141 (URN)10.1111/j.1742-4658.2009.07124.x (DOI)
    Available from: 2009-08-31 Created: 2009-08-31 Last updated: 2017-12-13Bibliographically approved
    3. A structural model of human steroid 11-betahydroxylase,CYP11B1, used to predict consequences of mutations
    Open this publication in new window or tab >>A structural model of human steroid 11-betahydroxylase,CYP11B1, used to predict consequences of mutations
    2009 (English)Article in journal (Other academic) Submitted
    Abstract [en]

    A prediction method has been developed to estimate the severity of amino acid residue exchanges in human steroid 11-beta-hydroxylase, CYP11B1, due to mutations in the corresponding gene. The prediction is based both on structural and on sequence dependent parameters. The method uses two approaches; one with general molecular property weights and one with a consensus voting strategy based upon distribution of molecular properties, which does not require any training. Both methods are tested on known mutations in CYP11B1 and result in 85% prediction accuracy. The consensus voting method is then further evaluated on 9 proteins with an average of 81% prediction accuracy. A server utilizing the results from the consensus voting on CYP11B1 is provided where the user can extract information about new mutants. A similar server is also provided for mutants in human steroid 21-hydroxylase (CYP21).

    Keywords
    CYP11B1, steroid 11-beta-hydroxylase, molecular modeling, structural prediction, mutations
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-51118 (URN)
    Available from: 2009-10-19 Created: 2009-10-19 Last updated: 2009-10-19Bibliographically approved
    4. Disruption of the GDNF Binding Site in NCAM DissociatesLigand Binding and Homophilic Cell Adhesion
    Open this publication in new window or tab >>Disruption of the GDNF Binding Site in NCAM DissociatesLigand Binding and Homophilic Cell Adhesion
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    2007 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 17, p. 12734-12740Article in journal (Refereed) Published
    Abstract [en]

    Most plasma membrane proteins are capable of sensing multiple cell-cell and cell-ligand interactions, but the extent towhich this functional versatility is founded on their modular design is less clear. We have identified the third immunoglobulin domain of the Neural Cell Adhesion Molecule (NCAM) as the necessary and sufficient determinant for its interaction with Glial Cell Line-derived Neurotrophic Factor (GDNF). Four charged contacts were identified by molecular modeling as the main contributors to binding energy. Their mutation abolished GDNF binding to NCAM but left intact the ability of NCAM tomediate cell adhesion, indicating that the two functions are genetically separable. The GDNF-NCAM interface allows complex formation with the GDNF family receptor α1, shedding light on the molecular architecture of a multicomponent GDNF receptor.

    Place, publisher, year, edition, pages
    Bethesda, MD: American Society for Biochemistry and Molecular Biology, 2007
    Keywords
    homology model, protein complex, interaction interface, mutagenesis
    National Category
    Bioinformatics and Systems Biology
    Identifiers
    urn:nbn:se:liu:diva-21306 (URN)10.1074/jbc.M701588200 (DOI)
    Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2017-12-13Bibliographically approved
    5. Functionally Important Amino Acids in the Arabidopsis Thylakoid Phosphate Transporter: Homology Modeling and Site-directed Mutagenesis
    Open this publication in new window or tab >>Functionally Important Amino Acids in the Arabidopsis Thylakoid Phosphate Transporter: Homology Modeling and Site-directed Mutagenesis
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    2010 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 49, no 30, p. 6430-6439Article in journal (Other academic) Published
    Abstract [en]

    The anion transporter 1 (ANTR1) from Arabidopsis thaliana, homologous to the mammalian SLC17 family, has recently been localized to the chloroplast thylakoid membrane. When expressed heterologously in Escherichia coli, ANTR1 mediates a Na+-dependent active transport of inorganic phosphate (Pi). The aim of this study was to identify amino acids involved in substrate binding/translocation by ANTR1 and in the Na+-dependence of its activity. A threedimensional structural model of ANTR1 was constructed using the crystal structure of glycerol-3-phosphate/phosphate antiporter (GlpT) from E.coli as a template. Based on this model and multiple sequence alignments, five highly conserved residues in plant ANTRs and mammalian SLC17 homologues have been selected for site-directed mutagenesis, namely Arg-120, Ser-124 and Arg-201 inside the putative translocation pathway, Arg-228 and Asp-382 exposed at the cytosolic surface of the protein. The activities of the wild type and mutant proteins have been analyzed using expression in E. coli and radioactive transport assays, and compared with bacterial cells carrying an empty plasmid. Based on Pi- and Na+-dependent kinetics, we propose that Arg-120, Arg-201 and Arg-228 are involved in binding and translocation of the substrate, Ser-124 functions as a periplasmic gate for Na+ ions, and finally Asp-382 participates in the turnover of the transporter via ionic interaction with either Arg-228 or Na+ ions. We also propose that the corresponding residues may have a similar function in other plant and mammalian SLC17 homologous transporters.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51119 (URN)10.1021/bi100239j (DOI)
    Note
    On the day of the defence day the status of this article was ManuscriptAvailable from: 2009-10-19 Created: 2009-10-19 Last updated: 2017-12-12Bibliographically approved
    6. A folding study on IAPP (Islet Amyloid Polypeptide) using molecular dynamics simulations
    Open this publication in new window or tab >>A folding study on IAPP (Islet Amyloid Polypeptide) using molecular dynamics simulations
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Amyloidosis is the largest group among the protein misfolding diseases, and includes well known diseases such as Alzheimer’s disease and type 2 diabetes. In the latter, islet amyloid is present in the pancreas in almost all individuals. Today, more than 25 different proteins have been isolated from amyloid deposits in human. Even though these proteins differ in size, charge and sequence they all have the capacity to assemble in to fibrillar structures with inseparable morphological appearance. Therefore, it can be assumed that the fibril process is based upon principles that are general for all proteins and knowledge derived from one protein can be used for other amyloid proteins. In this paper, we study the process of amyloid formation in parts of islet amyloid polypeptide (residues 18-29 and 11-37) by analyzing mutations using three different in silico methods. Finally, we use the methods to predict the amyloidogenic properties of the native IAPP and 16 variants thereof and compare the result with in vitro measurements. Using a consensus prediction of the three methods we managed to correctly classify all but two peptides. We have also given further evidence to the importance of S28P for inhibiting amyloid fibre formation, found evidence for antiparallel stacking, and identified important regions for beta sheet stability.

    Keywords
    IAPP, molecular modeling, amyloid, prediction, molecular dynamics, Monte Carlo
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-51120 (URN)
    Available from: 2009-10-19 Created: 2009-10-19 Last updated: 2010-01-14Bibliographically approved
    7. Virtual screening for ligands to human alcohol dehydrogenase 3
    Open this publication in new window or tab >>Virtual screening for ligands to human alcohol dehydrogenase 3
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Alcohol dehydrogenase 3 (ADH3) has been suggested a role in nitric oxide homeostasis due to its function as a S-nitrosoglutathione (GSNO) reductase. This has requested a modulator of the ADH3 activity for control of GSNO levels. Today virtual screenings are frequently used in drug discovery to dock and rank a large number of compounds. With molecular dockings of more than 40,000 compounds into the active site pocket of human ADH3 we ranked compounds with a novel method. Six top ranked compounds that were not known to interact with ADH3 were tested in vitro, where two showed substrate activity (9-decen-1-ol and dodecyltetraglycol), two showed inhibition capacity (deoxycholic acid and doxorubicin) and two did not have any detectable effect. For the substrates, site specific interactions and calculated binding scoring energies were determined with an extended docking simulation including flexible side chains of amino acids residues. The binding scoring energies correlated well with the logarithm of the substrates kcat over Km values. Furthermore, with these computational and experimental data three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs and in addition deoxycholic acids.

    Keywords
    Alcohol dehydrogenase, Enzyme kinetics, Molecular docking, Virtual screening
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-51121 (URN)
    Available from: 2009-10-19 Created: 2009-10-19 Last updated: 2010-01-14Bibliographically approved
  • 293.
    Carlsson, Jonas
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Persson, Bengt
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Investigating protein variants using structural calculation techniques2012In: Homology Modeling: Methods and Protocols / [ed] Andrew J. W. Orry and Ruben Abagyan, Springer, 2012, Vol. 857, p. 313-330Chapter in book (Other academic)
    Abstract [en]

    Knowledge about protein tertiary structure can guide experiments, assist in the understanding of structure-function relationships, and aid the design of new therapeutics for disease. Homology modeling is an in silico method that predicts the tertiary structure of an amino acid sequence based on a homologous experimentally determined structure. In, Homology Modeling: Methods and Protocols experts in the field describe each homology modeling step from first principles, provide case studies for challenging modeling targets and describe methods for the prediction of how other molecules such as drugs can interact with the protein. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Homology Modeling: Methods and Protocols guides scientists in the available homology modeling methods.

  • 294.
    Carlsson, Louise
    Linköping University, Department of Physics, Chemistry and Biology.
    Hierarchical Micro- and Nanostructured Superhydrophobic Surfaces to Reduce Fibrous Encapsulation of Pacemaker Leads: Nanotechnology in Practical Applications2008Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The purpose of this master’s thesis was to, by the use of nanotechnology, improve material properties of the biomedical polymer Optim™, used as the insulation of pacemaker leads. Improved material properties are required to reduce the extent of fibrous encapsulation of the leads. Today, laser ablation is used to be able to remove the pacemaker lead because of the fibrous tissue, which can cause the lead to adhere to vascular structures. Consequently, the laser ablation results in risks of damaging cardiovascular structures. Moreover, improved material properties are needed to reduce the friction at the surface and enhance the wear resistance. Large wearing occurs between the lead and the titanium pacemaker shell as well as lead against lead and the wearing can result in a damaged insulation, which in turn might result in removal of the device.

    To achieve these improved material properties a hierarchically micro- and nanostructured and superhydrophobic surface was fabricated and to enhance the wear resistance, nanocomposites with 1 wt % and 5 wt % added hydroxyapatite nanoparticles were fabricated. The surface structures were fabricated via hot embossing and plasma treatment and were characterised with atomic force microscopy, environment scanning electron microscopy and with contact angle measurements. To evaluate the biological response to the surfaces, adsorption of radioisotope labelled human serum albumin proteins and adhesion of the human fibroblast cell line MRC-5 were studied.

    The results show that a superhydrophobic surface, with contact angle as high as 170.0 ± 0.4 °, can be fabricated via hierarchically micro- and nanostructures on an Optim™ surface. The fabricated surface is more protein resistant and cell resistant compared to a smooth surface. The nanocomposites fabricated, especially the one with 5 wt % nanoparticles added, show an enhanced abrasive wear resistance compared to Optim™ without added nanoparticles. In conclusion, a hierarchically micro- and nanostructured superhydrophobic surface of the pacemaker lead seems promising for reducing the extent of fibrous encapsulation and by fabricating a nanocomposite, the abrasive wear damage of the lead insulation can be reduced.

  • 295.
    Carlsson, Rebecka
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Skogsväxters utbredning i relation till pH, latitud och trädsammansättning: Exkursion för ekologiundervisning2016Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This study investigated the impact of three edaphic factors on the distribution of forest plants in Sweden. Based on 2657 plots with 22 common species, Canonical Correspondence Analysis (CCA) and Generalized-linear-model (GLM) were performed with pH measurements in the top layer of the soil, latitude and deciduous tree proportion as explanatory variables. Variation of the species occurrence could to a substantial degree be explained by pH, latitude and proportion of timber volume of deciduous tree species. Furthermore, the majority of species were affected by the studied environmental variables. Therefore, these factors have an important role in the ecological interactions in the forest. All species also showed broad pH-niches with many occurrences spread out within the species entire pH-range. Finally, the study relates to educational science through designing a meaningful excursion for secondary school when teaching ecology.

  • 296.
    Carlsson, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Boxing for biodiversity: a long-term follow up of an artificial dead wood environment2015Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Today many saproxylic species are threatened because of habitat decline in Europe. Hollow trees represent a great part of the habitats that saproxylic species use. Since hollows takes a long time to develop, management actions are needed to prevent the extinction of saproxylic species. The aim of this study was to investigate the succession of saproxylic beetle species in artificial habitats in the form of wooden boxes. Wooden boxes were filled with a potential substrate and placed at different distances (0-1800 m) from oak hollow hot spots. In addition to the start mixture, four different additional substrates were added. In total, 4510 specimens of 114 saproxylic beetle species were sampled in 43 boxes over ten years. The specimens of tree-hollow species, wood rot species and nest species increased with 38% from the fourth to the final year but species richness decline from 47 to 29, respectively. A dead hen had a tendency for attracting more species but the small effect of different added substrates diminished over the years and had no significant effect on species richness after ten years. There was a higher similarity in species richness after ten years between the boxes and real hollow oaks. In conclusion, the artificial habitat developed into a more hollow like environment, with fewer but more abundant wood mould specialists, during ten years. This study clearly shows that the wooden boxes are used as habitats for saproxylic species as the boxes seems to develop into a more hollow-like habitat with time.

  • 297.
    Carlsson, Staffan
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Skillnader i mulmvolymer mellan fem trädslag i Östergötlands eklandskap2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Old hollow trees of oak contain a large amount of wood mould. Unfortunately, these trees have in the last century been greatly reduced in numbers. It has resulted in that species that depend on these habitats, saproxylic species, have become at risk to decrease in numbers or die out regionally. Previous studies have shown that the volume of wood mould is an important factor for occurrence and population size of saproxylic organisms. The aim of the present study was to examine how the volume of wood mould varies among ash (Fraxinus excelsior), lime (Tilia sp.), maple (Acer platanoides), aspen (Populus tremula) and oak (Quercus robur). The measurements were wood mould depth, internal cavity diameter, internal cavity height, circumference, and if white or brown rot was the dominating mould fungus. In total 23 ashes, 20 limes, 24 maples, 24 aspens and 21 oaks in the vicinity of Motala (Östergötland) were measured. The results show that there were significant differences between tree species concerning the volumes of wood mould. The oak accommodated larger volumes than the other species. The ash, however, had a larger volume than oak at the same circumference. The study shows ash could be a complement to the oak in conservation plans. Since the ash generally holds a larger volume then the oak at the same circumference, this implies the possibility that the ash can be suitable for saproxylic organisms at an earlier stage. In the isolated fragments of the landscape the possibility for survival may then increase for species that are dependent of these habitats.

  • 298.
    Carlsson, Staffan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bergman, Karl-Olof
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jansson, Nicklas
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Ranius, Thomas
    Department of Ecology, Swedish University of Agricultural Sciences, Box 7044, 750 07 Uppsala, Sweden.
    Milberg, Per
    Linköping University, Department of Physics, Chemistry and Biology, Ecology. Linköping University, Faculty of Science & Engineering.
    Boxing for biodiversity: evaluation of an artificiallycreated decaying wood habitat2016In: Biodiversity and Conservation, ISSN 0960-3115, E-ISSN 1572-9710, Vol. 25, no 2, p. 393-405Article in journal (Refereed)
    Abstract [en]

    Many saproxylic species are threatened in Europe because of habitat decline.Hollow trees represent an important habitat for saproxylic species. Artificial habitats mayneed to be created to maintain or increase the amount of habitat due to natural habitat decline.This study investigated the extent to which saproxylic beetles use artificial habitats in woodenboxes. The boxes were placed at various distances (0–1800 m) from known biodiversityhotspots with hollow oaks and studied over 10 years. Boxes were mainly filled with oak sawdust, oak leaves, hay and lucerne flour. In total, 2170 specimens of 91 saproxylic beetlespecies were sampled in 43 boxes. The abundance of species associated with tree hollows,wood rot and animal nests increased from the fourth to the final year, but species richnessdeclined for all groups. This study shows that wooden boxes can function as saproxylicspecies habitats. The artificial habitats developed into a more hollow-like environment duringthe decade long experiment with fewer but more abundant tree hollow specialists.

  • 299.
    Carrasco Del Amor, Ana Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Freitas, Sara
    Interdisciplinary Ctr Marine and Environm Res, Portugal.
    Urbatzka, Ralph
    Interdisciplinary Ctr Marine and Environm Res, Portugal.
    Fresnedo, Olatz
    Univ Basque Country, Spain.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Basque Country, Spain.
    Application of Bioactive Thermal Proteome Profiling to Decipher the Mechanism of Action of the Lipid Lowering 13(2)-Hydroxy-pheophytin Isolated from a Marine Cyanobacteria2019In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 17, no 6Article in journal (Refereed)
    Abstract [en]

    The acceleration of the process of understanding the pharmacological application of new marine bioactive compounds requires identifying the compound protein targets leading the molecular mechanisms in a living cell. The thermal proteome profiling (TPP) methodology does not fulfill the requirements for its application to any bioactive compound lacking chemical and functional characterization. Here, we present a modified method that we called bTPP for bioactive thermal proteome profiling that guarantees target specificity from a soluble subproteome. We showed that the precipitation of the microsomal fraction before the thermal shift assay is crucial to accurately calculate the melting points of the protein targets. As a probe of concept, the protein targets of 13(2)-hydroxy-pheophytin, a compound previously isolated from a marine cyanobacteria for its lipid reducing activity, were analyzed on the hepatic cell line HepG2. Our improved method identified 9 protein targets out of 2500 proteins, including 3 targets (isocitrate dehydrogenase, aldehyde dehydrogenase, phosphoserine aminotransferase) that could be related to obesity and diabetes, as they are involved in the regulation of insulin sensitivity and energy metabolism. This study demonstrated that the bTPP method can accelerate the field of biodiscovery, revealing protein targets involved in mechanisms of action (MOA) connected with future applications of bioactive compounds.

  • 300.
    Cassens, U.
    et al.
    Institute of Transfusion Medicine, University of Münster, D-48149 Münster, Germany.
    Lewinski, G.
    Unit of Surgery, Municipal Hospital, 38-300 Gorlice, Poland.
    Samraj, A. K.
    Institute of Molecular Medicine, University of Düsseldorf, D-40225 Düsseldorf, Germany.
    von Bernuth, H.
    Children´s University Clinic, Laboratory for Clinical Research, D-01307 Dresden, Germany.
    Baust, H.
    Department of Radiotherapy, University of Ulm, D-89070 Ulm, Germany.
    Khazaie, K.
    Department of Cancer Immunology and Aids, Dana Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts, MA 02115, USA.
    Los, Marek Jan
    Institute of Experimental Dermatology, University of Muenster, Germany.
    Viral modulation of cell death by inhibition of caspases2003In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 51, no 1, p. 19-27Article, review/survey (Refereed)
    Abstract [en]

    Caspases are key effectors of the apoptotic process. Some of them play important roles in the immune system, being involved in the proteolytic maturation of the key cytokines, including interleukin 1beta (IL-1beta) and IL-18. The latter directs the production of interferon gamma (IFN-gamma). Among pathogens, particularly viruses express various modulators of caspases that inhibit their activity by direct binding. By evading the apoptotic process, viruses can better control their production in the infected cell and avoid the attack of the immune system. Targeting the maturation of the key cytokines involved in the initiation of (antiviral) immune response helps to avoid recognition and eradication by the immune system. The three main classes of caspase inhibitors frequently found among viruses include serine proteinase inhibitors (serpins: CrmA/SPI-2), viral IAPs (vIAPs) and p35. Their molecular mechanisms of action, structures and overall influence on cellular physiology are discussed in the review below.

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