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  • 101.
    Elfstrand Corlin, Tinna
    et al.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    Kajonius, Petri J.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Kazemi, Ali
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    The impact of personality on person-centred care: a study of care staff in Swedish nursing homes2017Ingår i: International Journal of Older People Nursing, ISSN 1748-3735, E-ISSN 1748-3743, Vol. 12, nr 2, artikel-id e12132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim and objective: In this study, we explore how personal and situational factors relate to the provision of person-centred care (PCC) in nursing homes. Specifically, we focus on the relationship between the care staff's personality traits and provision of PCC and to what extent perceptions of the working environment influences this relationship.

    Background: The ultimate goal of elderly care is to meet the older person's needs and individual preferences (PCC). Interpersonal aspects of care and the quality of relationship between the care staff and the older person are therefore central in PCC.

    Design and methods: A cross-sectional Swedish sample of elderly care staff (= 322) completed an electronic survey including measures of personality (Mini-IPIP) and person-centred care (Individualized Care Inventory, ICI). A principal component analysis was conducted on the ICI-data to separate the user orientation (process quality) of PCC from the preconditions (structure quality) of PCC.

    Results: Among the five factors of personality, neuroticism was the strongest predictor of ICI user orientation. ICI preconditions significantly mediated this relationship, indicating the importance of a supportive working environment. In addition, stress was introduced as a potential explanation and was shown to mediate the impact of neuroticism on ICI preconditions.

    Conclusions: Personality traits have a significant impact on user orientation, and the perception of a supportive and stress free working environment is an important prerequisite for achieving high-quality person-centred elderly care.

    Implications for practice: Understanding how personality is linked to the way care staff interacts with the older person adds a new perspective on provision of person-centred elderly care.

  • 102.
    Elhakim, Rawan
    Högskolan i Skövde, Institutionen för biovetenskap.
    Urbana blomytor i Mariestads tätort: Kunskapsunderlag för tillämpad planering2019Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Antalet arter har minskat, och vår planet är i början av en sjätte massutrotning, detta beror främst på antropogena påverkan. Forskningen visar bland annat på en insektspopulationskollaps, eftersom 41 % av världens insekter har minskat varav en tredjedel är på väg mot utrotning. Detta tillstånd kan leda till ett katastrofalt sammanbrott i naturens ekosystem. Statliga verk ska ta fram riktlinjer för genomförandet av en handlingsplan gällande grön infrastruktur, agerande som underlag till länsstyrelsens hållbarhetsarbete. I samarbete med Mariestad kommun ska enkla och kostnadseffektiva medel, skapa underlag för praktiska åtaganden, och därmed öka den biologiska mångfalden i begränsande habitatområden. Detta sker genom förstärkningen av övergångsmiljön i stadsmiljöer, och undersökningen av gynnsamma spridningslänkar för pollinerare. I det här projektet har goda, förbättring- och potentiella blomytor analyserats för att teoretiskt öka konnektivitet för olika pollinatörer. Delresultat visar att det finns, 896991 m2 bristområde att förvalta för pollinerare med 50 m spridningsavstånd i Mariestad tätort. Konnektivitet kan då förmodas öka, med 41 % totalt för dessa pollinerare, och med 37 % för närmaste spridningsmöjlighet. Genom åtgärder såsom plantering av blomrika växter, slåtter, användningen av ekologisk växtjord, seedballs, och implementering av gröninfrastruktur, så kan bristområden omvandlas till oaser för pollinerande insekter. Detaljplaner kan ändras i antropogena syften, men avvägning mellan vad som är gynnsamt för människa eller natur, bör inte vara uteslutande av varandra. Därför är denna rapport en nulägesbeskrivning, men kommer med tiden bli missvisande. Det vore därför utmärkt att komplettera med en sannolikhetsanalys, och en specifik förvaltningsplan för respektive bristområde, med betoning på artsignifikans. 

  • 103.
    Engström, Erik
    Högskolan i Skövde, Institutionen för biovetenskap.
    Direct poly(A) RNA nanopore sequencing on the freshwater duck mussel Anodonta anatina following exposure to copper: A pilot study2019Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Aquatic ecotoxicology is the study of toxic chemicals and its effects on aquatic biological systems with the aim of minimising threats to human health and ensure self-sustained ecosystems. Freshwater bivalves are excellent sentinels for use in ecotoxilogical research due to their filter feeding properties, stationary lifestyle and inability to regulate body temperature. This project aimed to assess the feasibility and use of nanopore sequencing, a real-time single-molecule sequencing technology in comparative expression analysis by sequencing transcriptomic RNA from the freshwater mussel Anodonta anatina following exposure to copper. RNAs were extracted from 80 mg hepatopancreas tissue, followed by poly(A) RNA selection. Furthermore, the poly(A) RNA was used to construct a nanopore sequencing library. Sequencing a total amount of 560 ng poly(A) RNA over the course of two separate runs generated 239,448 reads, in which 75% of the reads were obtained during the first run (control) and 25% of the reads were obtained during the second run (case). The median read lengths ranged between 534-650 nucleotides, with a base call accuracy <90%. Due to the big differences in sequence data output between the two sequencing runs, the data was ineligible for comparative analysis. The findings conclude that nanopore sequencing is capable of generating longer read lengths when compared to other sequencing platforms. However, the technology is error-prone in terms of accurate base call identifications and relies on other platforms for error corrections. Future advances include de novo transcriptome assembly for efficient use of Anodonta anatina as a bioindicator in aquatic ecotoxicology.

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  • 104.
    Enroth, Helena
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Unilabs AB.
    Engstrand, L.
    Karolinska Institute and Science for Life Laboratory.
    Infectious Diseases: Helicobacter pylori2015Ingår i: Reference Module in Biomedical Sciences, Elsevier, 2015Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Abstract Helicobacter pylori infection is one of the most common human infections in the world. The bacteria cause peptic ulcer disease and their infection is an important factor for gastric cancer development. The bacteria are transmitted from person to person within families, with young children most often infected. The bacteria reside in the stomach for a lifetime if untreated by antimicrobial agents. Many virulence factors are known that contribute to the persistence of the bacteria in the stomach, and the bacteria harbors a pathogenicity island in its genome. The discovery of H. pylori as a cause of gastritis in the stomach led to the Nobel Prize in Physiology or Medicine 2005.

  • 105.
    Enroth, Helena
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Retz, Karolina
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Carl
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection2019Ingår i: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, nr 4, s. 249-258Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.

    Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.

    Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.

    Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

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  • 106.
    Enroth, Helena
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Unilabs AB.
    Wefer, Hugo
    Clinical genomics, Science for Life Laboratories.
    Ljungström, Lars
    Dept. of Infectious Diseases, Skaraborg Hospital Skövde.
    Tilevik, Diana
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap.
    NGS pilot study of E. coli ESBL from patients with suspected sepsis2015Konferensbidrag (Refereegranskat)
  • 107.
    Esborn, Ida
    Högskolan i Skövde, Institutionen för biovetenskap.
    Oxytocin and Trust: Biology, Neuroscience and Genetics of Trusting Behavior and Bonding in Human Adults2018Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Over the years the research regarding the versatility and variety of roles that oxytocin takes on in social behavior has grown substantially. The focus has mainly been on the reproductive functions of the hormone since it is released in the body during and after childbirth to help the mother connect with her offspring. More recent research shows that oxytocin influences higher-level social cognitive behaviors such as empathy, recognition, and trust. A connection between oxytocin and trust has been suggested, but not yet established. This thesis will further investigate if human trusting behavior is correlated with levels of oxytocin, and if so, to what degree. It seems that to what extent oxytocin affects human trust is due to personal and situational characteristics. By understanding how oxytocin can influence human trusting behavior researchers will get a better insight to persons suffering from conditions affecting their social abilities, such as anxiety, autism and schizophrenia. The study of oxytocin faces some problems, which will be brought up in this thesis. Among them is the unclear correlation between central and peripheral oxytocin levels. Another problem is how oxytocin interacts with other hormones in the body, and if the correlation with trusting behavior is due to hormones’ combined effects. More research in the field is needed to investigate how more complex human behaviors such as trust, can be modulated with the help of oxytocin. Further studies with broader and larger populations need to be conducted before any conclusion can be drawn.

  • 108.
    Eythorsdottir, Anita Bergros
    Högskolan i Skövde, Institutionen för biovetenskap.
    Application of isogenic normal and cancerous breast epithelial cell lines for drug testing: A new cancer drug in the making2019Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Abstract 

    Cancer is one of the leading causes of death world wide. A chemotherapy drug called Drug X has shown  promising results in the fight agains cancer. A drug called Drug Y has been used for decades however, patients that have previously been treaded with Drug Y may become resistant to the drug. This can lead to problems for patients that experience recurrence of cancer. Studies have shown that Drug X has a positive effect on both cancer and recurrence of cancer. Some cancer cells have a higher concentration of amino peptidases that both drugs use as a measure to invade cells. Drug X may be more potent than Drug Y and may work on cells that are resistant to Drug Y. Cells used in this experiment were D492 cells and D492HER2, obtained by inserting a HER2 gene into D492 cell.

    The aim with this study is to determine if cancer cells (D492HER2) express higher amino peptidases as well as obtaining difference in stress levels after receiving Drug X, with a side project of what influence Drug X has on Drug Y resistant cells (D492HER2Y). 

    A qPCR was used to measure the levels of certain amino peptidases followed by Western blot that unfortunately did not show any of the wanted amino peptidases. Reactive Oxygen Species indicated that cancerous cells that had been exposed to Drug X suffer from higher stress levels. In conclusion both qPCR and Reactive Oxygen Species show that Drug X has a DNA damage effect on the cells.

  • 109.
    Fabre, Kristin M.
    et al.
    Microphysiological Systems Center of Excellence, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Waltham, MA, United States.
    Delsing, Louise
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden / Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
    Colclough, Nicola
    Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Crowther, Damian C.
    Neuroscience, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Ewart, Lorna
    Microphysiological Systems Center of Excellence, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
    Utilizing microphysiological systems and induced pluripotent stem cells for disease modeling: a case study for blood brain barrier research in a pharmaceutical setting2019Ingår i: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 140, s. 129-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Microphysiological systems (MPS) may be able to provide the pharmaceutical industry models that can reflect human physiological responses to improve drug discovery and translational outcomes. With lack of efficacy being the primary cause for drug attrition, developing MPS disease models would help researchers identify novel targets, study mechanisms in more physiologically-relevant depth, screen for novel biomarkers and test/optimize various therapeutics (small molecules, nanoparticles and biologics). Furthermore, with advances in inducible pluripotent stem cell technology (iPSC), pharmaceutical companies can access cells from patients to help recreate specific disease phenotypes in MPS platforms. Combining iPSC and MPS technologies will contribute to our understanding of the complexities of neurodegenerative diseases and of the blood brain barrier (BBB) leading to development of enhanced therapeutics. © 2018

  • 110.
    Fagerlind, Magnus
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap.
    Stålhammar, Hans
    VikingGenetics, Skara.
    Olsson, Björn
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap.
    Klinga-Levan, Karin
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap.
    Expression of miRNAs in Bull Spermatozoa Correlates with Fertility Rates2015Ingår i: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 50, nr 4, s. 587-594Artikel i tidskrift (Refereegranskat)
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  • 111.
    Fasthén, Patrick
    Högskolan i Skövde, Institutionen för biovetenskap.
    The Virtual Self: Sensory-Motor Plasticity of Virtual Body-Ownership2014Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The distinction between the sense of body-ownership and the sense of agency has attracted considerable empirical and theoretical interest lately. However, the respective contributions of multisensory and sensorimotor integration to these two varieties of body experience are still the subject of ongoing research. In this study, I examine the various methodological problems encountered in the empirical study of body-ownership and agency with the use of novel immersive virtual environment technology to investigate the interplay between sensory and motor information. More specifically, the focus is on testing the relative contributions and possible interactions of visual-tactile and visual-motor contingencies implemented under the same experimental protocol. The effect of this is supported by physiological measurements obtained from skin conductance responses and heart rate. The findings outline a relatively simple method for identifying the necessary and sufficient conditions for the experience of body-ownership and agency, as studied with immersive virtual environment technology.

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  • 112.
    Fatima, Zahida
    et al.
    Pakistan Agricultural Research Council, Islamabad, Pakistan.
    Athar Khan, Muhammad
    University of Lahore, Pakistan.
    Ahmad, Mansur-ud-Din
    Department of Epidemiology and Public Health, University of Veterinary and Animal Sciences, Lahore, Pakistan.
    Muhammad, Khushi
    Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
    Khwaja, Khalid Naeem
    Pakistan Agricultural Research Council, Islamabad, Pakistan.
    Khan, Amjad
    Department of Epidemiology and Public Health, University of Veterinary and Animal Sciences, Lahore, Pakistan.
    Anwar, Zubair
    Högskolan i Skövde, Institutionen för biovetenskap.
    Ahad, Abdul
    Department of Microbiology and Veterinary and Public Health, Chittagong Veterinary and Animal Sciences University, Bangladesh.
    Mahmood, Altaf
    Livestock and Dairy Development Department, Punjab, Pakistan.
    Cross Sectional Survey of Live Bird Markets and Zoo Birds for Circulating Influenza Subtypes in Pakistan2017Ingår i: Pakistan Veterinary Journal, ISSN 0253-8318, E-ISSN 2074-7764, Vol. 37, nr 2, s. 185-189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In Pakistan, avian influenza surveillance has been both active and passive. Here, we present the results of a survey effort focusing solely on the live bird markets and wild bird species from different zoos and national parks to understand the impact of live bird markets on the spread of highly pathogenic avian influenza viruses. A cross sectional survey was conducted from Jan-Dec 2011 to identify and isolate the circulating avian influenza virus subtypes in live bird markets and wild birds from different localities in and around Islamabad Capital Territory. Swabs, tracheal tissues and sera samples were collected, screened and diagnosed by hemagglutination inhibition assay and RT-PCR. The highest seropositivity was recorded for H9 (100%) followed by H5 (89.4%) and H7 (72.3%). All 27 isolates were of the low pathogenic H9N2 subtypes and no viruses could be successfully isolated of subtype H5N1 or H7N7. The higher prevalence of H5N1 (89.4%) observed in the present study was an alarming threat; therefore, we suggested immediate control strategies against this emerging risk of H5N1 for human in live bird markets in Pakistan. The factors unveiled in this study will help in understanding the lapses in controlling persistent outbreaks of avian influenza in country.

  • 113.
    Fehrenbach, Stefan
    Högskolan i Skövde, Institutionen för biovetenskap.
    A modular approach to identify differentially expressed genes between men and women for inflammatory diseases2016Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Inflammatory diseases show large differences in susceptibility between men and women. In previous study, genes that showed different expression patterns between patients and healthy controls in males and females were identified using modules in disease-gene interaction networks. In this work, genes were identified using different methods based on gene expressions in public available data sets. By counting the occurrences of genes identified in the interaction network in our results, we showed that they greatly overlap with genes identified by our methods and that the disease gene-interaction networks are able to identify genes that can be identified in a gene expression based analysis as well. Gene expression analysis was implemented in an automatic pipeline, which was designed for a general use. Thereby, future research with similar problems can be simplified. The Rpackages limma and WGCNA were used to identify genes that showed differences in males and females and GO terms and KEGG pathways were used to search for enriched functions of those genes. Further, a difference between males and females was found for systemic lupus erythematosus and Sjögren’s syndrome data sets in the expression of genes belonging to interferon signaling. Interferons are currently examined as drug targets for SLE and a difference between men and women could lead to different results of such a medication. However, the identified genes showed changes in expressions between patients and controls for both men and women. This supports a beneficial effect of such drugs in men and women.

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  • 114.
    Feilhauer, Diana
    Högskolan i Skövde, Institutionen för biovetenskap.
    Measuring Emotions in Dreams: Methodological Challenges2015Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Although emotions are a natural component of dream experiences, a lack of consensus prevails in research literature concerning the specific characteristics of emotional dream experiences. The aim of this study was to investigate if and to what extent this lack of convergence among studies stems from whether dream emotions are self- or externally rated - forty-four healthy participants (16 males and 28 females; mean age = 26.93, range = 19 - 40) kept a home dream diary for three consecutive weeks, and daily rated their emotional experiences in dreams with the Swedish modified Differential Emotions Scale (smDES; Fredrickson, 2013). Two external judges rated emotions in the same 552 home dream reports using the same scale. Results obtained with the two methods differed in that the self-ratings, compared to external ratings, revealed: (a) more emotional dreams; (b) more positive than negative emotions per dream (with the ratio being relatively balanced); (c) a relatively more balanced proportion of positive and negative emotions, while the external ratings revealed more negative than positive emotions per dream. The results suggest that this is mostly due to the underrepresentation of positive emotions with external ratings. Thus, the results continue to question the extent of convergence between self- and external ratings when investigating emotional dream contents, and bring to attention the importance of methodological aspects when investigating dream emotions.

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    Measuring Emotions in Dreams: Methodological Challenges
  • 115.
    Fernandes, Ricardo A.
    et al.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom / Department of Molecular and Cellular Physiology, Department of Structural Biology, Stanford University, United States.
    Ganzinger, Kristina A.
    Department of Chemistry, University of Cambridge, United Kingdom / Living Matter Department, Physics of Cellular Interactions Group, AMOLF, Amsterdam, Netherlands.
    Tzou, Justin C.
    Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, United States.
    Jönsson, Peter
    Department of Chemistry, University of Cambridge, United Kingdom / Department of Chemistry, Lund University, Sweden.
    Lee, Steven F.
    Department of Chemistry, University of Cambridge, United Kingdom.
    Palayret, Matthieu
    Department of Chemistry, University of Cambridge, United Kingdom.
    Santos, Ana Mafalda
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Carr, Alexander R.
    Department of Chemistry, University of Cambridge, United Kingdom.
    Ponjavic, Aleks
    Department of Chemistry, University of Cambridge, United Kingdom.
    Chang, Veronica T.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom / Neurobiology Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
    Macleod, Charlotte
    Department of Chemistry, University of Cambridge, United Kingdom.
    Lagerholm, B. Christoffer
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Lindsay, Alan E.
    Mathematics Department, University of British Columbia, Vancouver, Canada.
    Dushek, Omer
    Sir William Dunn School of Pathology, University of Oxford, United Kingdom / Wolfson Centre for Mathematical Biology, University of Oxford, United Kingdom.
    Tilevik, Andreas
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. School of Bioscience, University of Skövde, Sweden.
    Davis, Simon J.
    Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom / Medical Research Council Human Immunology Unit, John Radcliffe Hospital, University of Oxford, United Kingdom.
    Klenerman, David
    Department of Chemistry, University of Cambridge, United Kingdom.
    A cell topography-based mechanism for ligand discrimination by the T cell receptor2019Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, nr 28, s. 14002-14010Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes. 

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  • 116.
    Fioretto, Paola
    et al.
    Department of Medicine, University of Padova, Padova, Italy.
    Del Prato, Stefano
    Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy.
    Buse, John B.
    Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Goldenberg, Ronald
    LMC Diabetes & Endocrinology, Thornhill, Canada.
    Giorgino, Francesco
    Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy.
    Reyner, Daniel
    AstraZeneca, Gaithersburg, Maryland, USA.
    Langkilde, Anna Maria
    AstraZeneca, Gothenburg, Sweden.
    Sjöstrom, C. David
    AstraZeneca, Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. AstraZeneca, Gothenburg, Sweden.
    Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study2018Ingår i: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, nr 11, s. 2532-2540Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Dapagliflozin is a selective inhibitor of sodium glucose co-transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45-59 mL/min/1.73 m(2); chronic kidney disease [CKD] stage 3A). Materials and methods: In this double-blind, parallel group, Phase 3 study (NCT02413398, ) patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N = 160) or matching placebo (N = 161) for 24 weeks. Randomization was stratified by pre-enrolment glucose-lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24. Results: At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], -0.34% [-0.53, -0.15]; P < 0.001), body weight (difference [95% CI], -1.25 kg [-1.90, -0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], -0.9 mmol/L [-1.5, -0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], -3.1 mmHg [-6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (-2.49 mL/min/1.73 m(2) [-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61 mL/min/1.73 m(2) [-1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported. Conclusions: The findings of this study (NCT02413398, ) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.

  • 117.
    Fjordstig, Andréas
    Högskolan i Skövde, Institutionen för biovetenskap.
    Separating Post-perceptual Processes From Auditory Awareness: An Electrophysiological Study With a No-response Task2019Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Two theories of consciousness have different ideas about when consciousness happens and what neural processes enable conscious experience. The recurrent processing theory supports an early onset of consciousness caused by recurring loops of information between sensory areas. Contrary to this belief, the global workspace theory claims that consciousness appears later, through global recurrent loops of information between sensory and higher order brain areas such as the visual cortex and frontoparietal areas. Electrophysiological studies have found an event-related negativity arising in primary visual areas around 200 ms that correlates to awareness. This activity suits the predictions of an early onset of consciousness made by the recurrent processing theory. It is followed by a later positive amplitude appearing around 400 ms. This activity is in line with predictions made by the global workspace theory. The current study transition from visual to auditory awareness research in order to find the neural correlates of consciousness in audition. A sound detection task with tones calibrated to each participants threshold value was used in the experiment and two electrophysiological measurements of auditory awareness were found. An auditory awareness negativity that appears around 200 ms after stimulus onset and a late positivity appearing around 400 ms. Researchers disagree about if these event-related potentials correlate with awareness or unrelated cognitive mechanisms. In order to solve this problem, the current experiment was devised to test if they were affected by response conditions. A no-response paradigm with reversed response conditions was used to separate pre- and post-conscious mechanisms from the auditory awareness negativity and the late positivity. Results showed that auditory awareness negativity was independent of response condition and thus free from post-perceptual processes. The late positivity amplitude seems to be dependent on response condition but the result was inconclusive.

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  • 118.
    Fors, John
    Högskolan i Skövde, Institutionen för biovetenskap.
    Effectiveness of reduced-dose efavirenz in hiv therapy considering patient adherence2012Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Antiretroviral drugs have revolutionized HIV care and enabled better management of the infection thus allowing patients survive for many years. One proposed approach to increase access to such drugs in sub-Saharan Africa is to use of a reduced-dose alternative of the drug efavirenz, with 400 mg rather than regular 600 mg dose. This effectively would provide medication for 50 percent more persons with the same amount of active ingredient. However, antiretroviral drugs require high patient adherence to achieve intended therapeutic effect, and it is unclear if a reduced-dose therapy would have sufficient efficacy, and if it would lead to an increased risk of viral resistance.

    The time profile of drug plasma concentration and corresponding long-term viral load was estimated using integrated population PK/PD simulations, with model parameters based on selected research studies. The results suggest a reduced dose 400 mg, rather than 600 mg regular dose, efavirenz in HIV therapy would place strict demands on patients to maintain very high adherence levels, at least 80-90 percent, to maintain sufficient drug concentration in blood plasma, and to minimize risk of viral failure. However, it is relatively rare for HIV therapy programs in sub-Saharan Africa to consistently achieve such high adherence levels. In addition, if patients are co-administered rifampin, a drug widely used in TB care, this increases hepatic metabolism and plasma clearance rate, resulting in further reduced average drug plasma concentration. These findings suggest a reduced dose efavirenz treatment alternative may be most (only) relevant for patient categories expected to maintain high adherence; and in particular among persons who have been confirmed to have CYP2B6 genotype consistent with inherently lower drug metabolism. At usual adherence levels it is estimated a reduced dose alternative may increase the share of patients at risk of viral failure by 5 to 15 percent vs. regular dose of 600 mg.

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  • 119.
    Freij, Mathilda
    Högskolan i Skövde, Institutionen för biovetenskap.
    Restaureringens roll gällande Hornborgasjöns förmåga till kväve- och fosforretention2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Idag är Hornborgasjön en av Europas viktigaste fågelsjöar men det har inte alltid varit så. Innan natur och kulturvårdsintressen värnades utdikades sjön till förmån för jordbruket och lämnades att växa igen. I början och mitten av 90-talet påbörjades och färdigställdes en omfattande restaurering av sjön som i kort innebar en höjning av vattenståndet och en ökad sjöareal.

     

    Under många år har man regelbundet testat vattenkvaliteten i Hornborgasjöns inlopp och utlopp. Rapporten syftar till att använda en del av dessa data till att undersöka sjöns retention av kväve och fosfor samt om denna förändrats i och med restaureringen. Detta gjordes med hjälp av medeldifferenserna av totalkväve och totalfosfor mellan in- och utlopp. Medeldifferenserna ger en indikation på om mindre halter försvinner ut ur sjön än som kommer in. På så sätt kan medeldifferenserna representera de halter som stannar kvar i sjön, som retenteras av sjön.

     

    Analysen visar att medeldifferenserna av totalkväve mellan in- och utlopp har ökat efter restaureringen. Vad gäller medeldifferenserna av totalfosfor däremot kan ingen skillnad visas vid de flesta av testerna och ett utav dem visar att medeldifferenserna av totalfosfor mellan in- och utlopp signifikant minskat. Dessa resultat indikerar att restaureringen av Hornborgasjön ökat dess retenterande förmåga vad gäller kväve men inte fosfor. Dock krävs mer omfattande studier med säkrare metoder för att kunna styrka dessa resultat.

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    Restaureringens roll gällande Hornborgasjöns förmåga till kväve- och fosforretention
  • 120.
    Frisk, Mikael
    et al.
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Jonsson, Annie
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Sellman, Stefan
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Flisberg, Patrik
    The Forestry Research Institute of Sweden, Uppsala, Sweden.
    Rönnqvist, Mikael
    Département de génie mécanique, Université Laval, Québec, Canada.
    Wennergren, Uno
    Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 3, artikel-id e0193223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact.

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  • 121.
    Frost, Morgan
    Högskolan i Skövde, Institutionen för biovetenskap.
    Social perception in Autism: An eye tracking and pupillometric study2018Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Typically developing humans innately place subjective value on social information and orient attention to it. This can be shown through eye tracking and pupillometry, a method used to show attentional engagement. Social brain development and social preference is present from infancy, and is thought to rely on a carefully balanced network of neurotransmitters and neural connections. Autism Spectrum Disorder (ASD) presents altered neural systems which cause individuals to perceive and process social information differently, but the neurophysiology of this difference remains unclear. Previous research shows atypical gaze patterns, hyperarousal, and lack of orienting to social stimuli in ASD. Since autism is highly comorbid and shares traits with other neurodevelopmental disorders, it is difficult to distinguish aspects of these social processing differences. This study used a group of 35 neuropsychiatric patients to investigate how individuals with autism process social and non-social scenes. Eye tracking and pupillometry measures were collected while participants observed images of natural scenes with or without a person. Participants with autism did not show a pupillary response to social images and were slower to fixate on the face  region than the other participants. Additionally there were correlations between clinical measures of social functioning and the length of time it took to fixate to faces. The results highlight important distinctions of social processing in autism. This thesis proposes a new perspective of looking at the social deficits present in autism spectrum disorder. It suggests reframing the current discussion from two leading hypotheses to a unified approach and formally considering the limitations of differing types of stimuli.

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  • 122.
    Frost, Morgan
    Högskolan i Skövde, Institutionen för biovetenskap. Gillberg Neuropsychiatry Centre.
    Social Perception in Autism: An eye-tracking and pupillometric study2018Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Typically developing humans innately place subjective value on social informa- tion and orient attention to it. This can be shown through eye tracking and pupillometry, a method used to show attentional engagement. Social brain de- velopment and social preference is present from infancy, and is thought to rely on a carefully balanced network of neurotransmitters and neural connections. Autism Spectrum Disorder (ASD) presents altered neural systems which cause individuals to perceive and process social information di↵erently, but the neuro- physiology of this di↵erence remains unclear. Previous research shows atypical gaze patterns, hyperarousal, and lack of orienting to social stimuli in ASD. Since autism is highly comorbid and shares traits with other neurodevelopmental dis- orders, it is dicult to distinguish aspects of these social processing di↵erences. This study used a group of 35 neuropsychiatric patients to investigate how in- dividuals with autism process social and non-social scenes. Eye tracking and pupillometry measures were collected while participants observed images of nat- ural scenes with or without a person. Participants with autism did not show a pupillary response to social images and were slower to fixate on the face re- gion than the other participants. Additionally there were correlations between clinical measures of social functioning and the length of time it took to fixate to faces. The results highlight important distinctions of social processing in autism. This thesis proposes a new perspective of looking at the social deficits present in autism spectrum disorder. It suggests reframing the current discus- sion from two leading hypotheses to a unified approach and formally considering the limitations of di↵ering types of stimuli.

  • 123.
    Frändén, Philip
    Högskolan i Skövde, Institutionen för biovetenskap.
    Neural Correlates of Heart Rate Variability: Threat and Safety Perception2018Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The connection between the heart and the brain was coined 150 years ago by Claude Bernard and has since then been an interesting topic of research. Scientists have for many years searched for biomarkers of stress and health to map the current status of the organism. Heart rate variability (HRV) has been presented as an emerging objective and promising marker to achieve just this. HRV refers to the beat-to-beat variations in heart rate (HR) and is thought to be a useful signal in understanding and providing valuable information of the autonomic nervous system (ANS). HRV has also been proposed as a marker of stress and health by sharing neural correlates and functions with several executive functions. This thesis identified several regions, including the ventromedial prefrontal cortex and the amygdala, in which significant associations across several studies were found between threat and safety perception, emotional regulation and HRV. This suggest that HRV may function as an index of the brain mechanism and structures that guide and govern adaptive functions and thus, provide researchers with valuable information regarding the stress and health of an organism. Two major theoretical frameworks, which articulate and explain the role of HRV as an indicator of individuals ability to adapt to environmental changes and cope under stress is presented. HRV can also be used in practice in several ways and a growing and promising field of application is HRV biofeedback.

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  • 124.
    Förster, Jona
    Högskolan i Skövde, Institutionen för biovetenskap.
    ERP and MEG Correlates of Visual Consciousness: An Update2019Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Two decades of event-related potential (ERP) research have established that the most consistent correlates of the onset of visual consciousness are the early visual awareness negativity (VAN), a negative component in the N2 time range over posterior electrode sites, and the late positivity (LP), a positive component in the P3 time range over fronto-parietal electrode sites. A review by Koivisto & Revonsuo (2010) had looked at 39 studies and concluded that the VAN is the earliest and most reliable correlate of visual phenomenal consciousness, whereas the LP probably reflects later processes associated with reflective/access consciousness. However, an “early” vs. “late” debate still persists. This thesis provides an update to that earlier review. All ERP and MEG studies that have appeared since 2010 and directly compared ERPs of aware and unaware conditions are considered. The result corroborates the view that VAN is the earliest and most consistent signature of visual phenomenal consciousness, and casts further doubt on the LP as an ERP correlate of consciousness. Important new methodological, empirical, and theoretical developments in the field are described, and the empirical results are related to the theoretical background debates.

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  • 125.
    Förster, Jona
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Department of Psychology, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    ERP and MEG correlates of visual consciousness: The second decade2020Ingår i: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 80, artikel-id 102917Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The first decade of event-related potential (ERP) research had established that the most consistent correlates of the onset of visual consciousness are the early visual awareness negativity (VAN), a posterior negative component in the N2 time range, and the late positivity (LP), an anterior positive component in the P3 time range. Two earlier extensive reviews ten years ago had concluded that VAN is the earliest and most reliable correlate of visual phenomenal consciousness, whereas LP probably reflects later processes associated with reflective/access consciousness. This article provides an update to those earlier reviews. ERP and MEG studies that have appeared since 2010 and directly compared ERPs between aware and unaware conditions are reviewed, and important new developments in the field are discussed. The result corroborates VAN as the earliest and most consistent signature of visual phenomenal consciousness, and casts further doubt on LP as an ERP correlate of phenomenal consciousness. 

  • 126.
    Garcia, Danilo
    et al.
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden.
    Persson, Björn
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Network for Empowerment and Well-Being, Sweden / Department of Psychology, University of Turku, Finland.
    Al Nima, Ali
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Network for Empowerment and Well-Being, Sweden.
    Gruneau Brulin, Joel
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Rapp-Ricciardia, Max
    Blekinge Center of Competence, Blekinge County Council, Karlskrona, Sweden / Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden.
    Kajonius, Petri J.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Gothenburg, Gothenburg, Sweden / Network for Empowerment and Well-Being, Sweden / Department of Behavioral Sciences, University West, Sweden.
    IRT analyses of the Swedish Dark Triad Dirty Dozen2018Ingår i: Heliyon, ISSN 2405-8440, Vol. 4, nr 3, artikel-id e00569Artikel i tidskrift (Refereegranskat)
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  • 127.
    Gerafi, Joel
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Long-term functional outcome after ischemic stroke: Prognostic value of early identification of neglect and aphasia2017Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
  • 128.
    Gerafi, Joel
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / The Skaraborg Institute for Research and Development, Skövde, Sweden.
    Samuelsson, H.
    Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Viken, J. I.
    Department of Psychology, Faculty of Social Sciences, University of Gothenburg, Gothenburg, Sweden / Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blomgren, C.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Claesson, L.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Kallio, Sakari
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Jern, C.
    Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blomstrand, C.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Jood, K.
    Institute of Neuroscience and Physiology,The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Neurology, The Sahlgrenska University Hospital, Gothenburg, Sweden.
    Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke2017Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, nr 11, s. 1407-1415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Visuospatial inattention (VSI) and languageimpairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. Methods: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1–5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian StrokeScale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. Results: The regression model significantly explained variance in the modified Rankin scale (R2= 0.435, P < 0.001) and identified VSI (P=0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for FrenchayActivities Index was also significant (R2= 0.269, P < 0.001) with VSI(P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. Conclusions: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

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  • 129.
    Gerafi, Joel
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Faculty of Social Sciences, Department of Psychology, University of Gothenburg, Sweden / Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden / The Skaraborg Institute for Research and Development, Skövde, Sweden.
    Samuelsson, Hans
    Faculty of Social Sciences, Department of Psychology, University of Gothenburg, Sweden / Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Viken, Jo I.
    Faculty of Social Sciences, Department of Psychology, University of Gothenburg, Sweden / Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Jern, Christina
    Department of Laboratory Medicine, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Blomstrand, Christian
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Jood, Katarina
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden / Department of Neurology, The Sahlgrenska University Hospital, Gothenburg, Sweden.
    The presence and prediction of lateralized inattention 7 years post-stroke2020Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 141, nr 5, s. 423-430Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Lateralized inattention is a typical sign of neglect and related to poor functional outcome. Knowledge of the long-term course of this phenomenon is limited. The purpose of this study was to investigate presence and predictors for signs of lateralized inattention 7 years after stroke. Methods: From a cohort of acute ischemic stroke patients, aged 18-69 years (n = 297), a consecutive series of 188 survivors without recurrent stroke at follow-up 7 years later were included. Within the first week after stroke onset, stroke severity was assessed according to the Scandinavian Stroke Scale. Target omissions, asymmetry of omissions, and perceptual speed according to Star- and Letter Cancellation Tests were also assessed. Presence of lateralized inattention at the 7-year follow-up was investigated with the Star- and Letter Cancellation Tests and with the neglect item in the National Institutes of Health Stroke Scale. Results: At the follow-up, 22 (11.7%) participants had lateralized inattention and the multivariable regression showed that independent significant baseline predictors were total omissions in target cancellations (P <.001) and inferior baseline performance on visual processing speed (P =.008). Conclusion: About one of ten individuals exhibited signs of lateralized inattention 7 years after stroke. Baseline performance in perceptual processing speed and target omissions independently predicted presence of late signs of lateralized inattention. This is the first time processing speed is recognized as a significant predictor of lateralized inattention several years after the stroke incidence, indicating that the longitudinal course of processing speed following stroke is a critical subject for future research. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

  • 130.
    Ghannoum, Salim
    Högskolan i Skövde, Institutionen för biovetenskap.
    Characterizing sub-populations of myxoid liposarcoma cells using a multi-algorithmic pipeline for analyzing single-cell RNA sequencing data2018Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    All tumors are characterized by intratumor heterogeneity at varying degrees. Cancer stem cells have been put forward to be an essential element that promotes heterogeneity. Myxoid liposarcoma, which is a lipogenic cancer that develops in deep soft connective tissues, is characterized by intermediate intratumor heterogeneity. Despite recent therapeutic advances, the post-treatment recurrence rate remains relatively high. Identifying sub-populations of myxoid liposarcoma tumors can help in characterizing their molecular signatures and tumorigenic capabilities leading to developing better therapeutics. Single-cell transcriptomic approaches can highlight deviations in gene expression patterns among different subpopulations within the tumor. In this study, a multi-algorithmic pipeline was developed to make a fast, simple and efficient process for characterizing cellular sub-populations of cancer cells and gain insight about the molecular signature of the cancer stem sub-population. This pipeline consists of four successive steps, read counts’ pre-processing, cellular clustering and pseudotemporal ordering, defining differential expressed genes and defining biomarker genes. The results showed a harmonic integration between the algorithms that constitute the backbone of the proposed pipeline leading to a reduction in the limitations of some of these algorithms. The outcome of this study is a panel of 33 genes nominated as possible biomarkers for stemness and aggressiveness. To optimize and validate these biomarker candidates, further investigations are required. Moreover, additional functional coupling analysis is necessary to nominate biomarkers for each of the sub-populations based on the defined differential expressed genes.

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    Salim Ghannoum Master Thesis
  • 131.
    Ghosheh, Nidal
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Küppers-Munther, Barbara
    Takara Bio Europe AB, Gothenburg, Sweden.
    Asplund, Annika
    Takara Bio Europe AB, Gothenburg, Sweden.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Björquist, Petter
    VeriGraft AB, Gothenburg, Sweden.
    Andersson, Tommy B.
    Cardiovascular Renal and Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Late Stage Cardiovascular, Renal, and Metabolism, R&D BioPharmaceuticals, AstraZeneca, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Human Pluripotent Stem Cell-Derived Hepatocytes Show Higher Transcriptional Correlation with Adult Liver Tissue than with Fetal Liver Tissue2020Ingår i: ACS Omega, ISSN 2470-1343, Vol. 5, nr 10, s. 4816-4827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 

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  • 132.
    Ghosheh, Nidal
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Asplund, Annika
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Edsbagge, Josefina
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Andersson, Tommy B.
    Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Björquist, Petter
    NovaHep Aktiebolaget, Gothenburg, Sweden.
    Andersson, Christian X.
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. AstraZeneca Research and Development, Global Medicines Development Cardiovascular and Metabolic Diseases Global Medicines Development Unit, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue2017Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 49, nr 8, s. 430-446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte differentiation. Using functional annotation, pathway and protein interaction network analyses, we observed the grouping of differentially expressed genes in specific clusters representing typical developmental stages of hepatic differentiation. In addition, we identified hub proteins and modules that were involved in the cell cycle process at early differentiation stages. We also identified hub proteins that differed in expression levels between hPSC-HEP and the liver tissue controls. Moreover, we identified a module of genes that were expressed at higher levels in the liver tissue samples than in the hPSC-HEP. Considering that hub proteins and modules generally are essential and have important roles in the protein-protein interactions, further investigation of these genes and their regulators may contribute to a better understanding of the differentiation process. This may suggest novel target pathways and molecules for improvement of hPSC-HEP functionality, having the potential to finally bring this technology to a wider use.

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    Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue
  • 133.
    Ghosheh, Nidal
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olsson, Björn
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Edsbagge, Josefina
    Takara Bio Europe AB, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe AB, Gothenburg, Sweden.
    Van Giezen, Mariska
    Takara Bio Europe AB, Gothenburg, Sweden.
    Asplund, Annika
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Andersson, Tommy B.
    AstraZeneca R&D, CVMD DMPK, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Björquist, Petter
    NovaHep AB, Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. AstraZeneca R&D, GMD CVMD GMed, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines2016Ingår i: Stem Cells International, ISSN 1687-9678, Vol. 2016, artikel-id 8648356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

  • 134.
    Godoy, Patricio
    et al.
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany / Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile.
    Schmidt-Heck, Wolfgang
    Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, Jena, Germany.
    Natarajan, Karthick
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Lucendo-Villarin, Baltasar
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Szkolnicka, Dagmara
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Asplund, Annika
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
    Björquist, Petter
    NovaHep AB, Gothenburg, Sweden.
    Widera, Agata
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Stöber, Regina
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Campos, Gisela
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Hammad, Seddik
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Sachinidis, Agapios
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Chaudhari, Umesh
    University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
    Damm, Georg
    Charité University Medicine Berlin, Department of General-, Visceral- and Transplantation Surgery, Berlin, Germany.
    Weiss, Thomas S.
    Center for Liver Cell Research, Department of Pediatrics and Juvenile Medicine, University of Regensburg Hospital, Regensburg, Germany.
    Nüssler, Andreas
    Eberhard Karls University Tübingen, BG Trauma Center, Siegfried Weller Institut, Tübingen, Germany.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Edlund, Karolina
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Küppers-Munther, Barbara
    Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden.
    Hay, David C.
    MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Hengstler, Jan G.
    IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
    Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells2015Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 63, nr 4, s. 934-942Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.

    METHODS: Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.

    RESULTS: Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The "unwanted" intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.

    CONCLUSIONS: The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation.

  • 135.
    Gopalan Nair, Rekha
    Högskolan i Skövde, Institutionen för biovetenskap.
    Cloning and functional analysis of an arsB gene responsible for arsenic sequestration in Lysinibacillus sphaericus2016Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
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  • 136.
    Grankvist, Gunne
    et al.
    Department of Social and Behavioural Studies, University West, Trollhättan, Sweden.
    Kajonius, Petri
    Department of Social and Behavioural Studies, University West, Trollhättan, Sweden.
    Persson, Björn
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    The Relationship between Mind-Body Dualism and Personal Values2016Ingår i: International Journal of Psychological Studies, ISSN 1918-7211, E-ISSN 1918-722X, Vol. 8, nr 2, s. 126-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dualists view the mind and the body as two fundamental different “things”, equally real and independent of each other. Cartesian thought, or substance dualism, maintains that the mind and body are two different substances, the non-physical and the physical, and a causal relationship is assumed to exist between them. Physicalism, on the other hand, is the idea that everything that exists is either physical or totally dependent of and determined by physical items. Hence, all mental states are fundamentally physical states. In the current study we investigated to what degree Swedish university students’ beliefs in mind-body dualism is explained by the importance they attach to personal values. A self-report inventory was used to measure their beliefs and values. Students who held stronger dualistic beliefs attach less importance to the power value (i.e., the effort to achieve social status, prestige, and control or dominance over people and resources). This finding shows that the strength in laypeople’s beliefs in dualism is partially explained by the importance they attach to personal values

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  • 137.
    Granéli, Cecilia
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Brolén, Gabriella
    Discovery Sciences, IMED Biotech Unit, AstraZeneca Gothenburg, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Global Medicines Development, CVRM, AstraZeneca Gothenburg, Mölndal, Sweden.
    Diabetic Cardiomyopathy Modelling Using Induced Pluripotent Stem Cell Derived Cardiomyocytes: Recent Advances and Emerging Models2019Ingår i: Stem Cell Reviews, ISSN 1550-8943, E-ISSN 1558-6804, Vol. 15, nr 1, s. 13-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 138.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Finland.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Visual features and perceptual context modulate attention towards evolutionarily relevant threatening stimuli: Electrophysiological evidence2019Ingår i: Emotion, ISSN 1528-3542, E-ISSN 1931-1516, Vol. 19, nr 2, s. 348-364Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 139.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Finland.
    Castellotti, Serena
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Petrizzo, Irene
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Benedetti, Viola
    Department of Psychology, University of Turku, Finland / Department of Psychology, University of Florence, Italy.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Processing of natural scenery is associated with lower attentional and cognitive load compared with urban ones2019Ingår i: Journal of Environmental Psychology, ISSN 0272-4944, E-ISSN 1522-9610, Vol. 62, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 140.
    Grassini, Simone
    et al.
    Department of Psychology, University of Turku, Finland.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Turku, Finland /Turku Brain and Mind Center, University of Turku, Turku, Finland.
    Souchet, Jérémie
    Station D'Ecologie Théorique et Expérimentale Du CNRS, France.
    Aubret, Fabien
    Station D'Ecologie Théorique et Expérimentale Du CNRS, France.
    Segurini, Giulia V.
    Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland.
    Pattern matters: Snakes exhibiting triangular and diamond-shaped skin patterns modulate electrophysiological activity in human visual cortex2019Ingår i: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 131, s. 62-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 141.
    Grundkvist, Anders
    Högskolan i Skövde, Institutionen för biovetenskap.
    Tillväxt av alger i Vänern: Abiotiska faktorers inverkan på algtillväxt i Vänern2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
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  • 142.
    Gusevac, Stela
    Högskolan i Skövde, Institutionen för biovetenskap.
    Emotion Regulation: Functional neuroimaging studies of cognitive reappraisal2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The importance of investigating Emotion Regulation (ER) may be self-evident, given that emotions have a substantial impact on our daily lives. ER encompasses set of processes that people go through in order to cultivate their feelings that arise at the moment and produce some response. Brain-imaging studies of ER have broadly focused on examining cognitive strategies, such as reappraisal, in order to understand underlying variables that contribute to the development of this particular process of emotions. The main focus in this paper was to summarize some of the observation done by functional Magnetic Resonance Imaging (fMRI) on neural processes underlying cognitive reappraisal. Furthermore, the paper will discuss some of these experiments that have been made through the last 15 years in the field where indications have been somewhat confusing when it comes to certain aspects of presented data, especially in comparison with other studies. Finally, a brief overview and some of the significant contributions, such as a process model of ER, to the field of ER have been presented and discussed. Cognitive reappraisal has been shown to effectively down-regulate subjective emotional experience. Even though many studies have been performed in measuring brain-activity when engaging in cognitive reappraisal, a unified and accepted agreement has yet not been found. In broader terms, brain-responses when engaging in cognitive reappraisal seem to operate in a particular manner where different parts of prefrontal and parietal cortex execute control over subcortical regions, such as amygdala.

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  • 143.
    Haglund, Cecilia
    Högskolan i Skövde, Institutionen för biovetenskap.
    The relationships of empathy, oxytocin, and depression2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Empathy, oxytocin, and depression are three subjects that are widely researched. Empathy means experiencing or understanding the emotions of an individual who is being observed. Oxytocin has frequently been shown to have a connection to lactation and labor. Depression is a common sickness that results in malfunctioning, suffering, and a shorter life. The mutual relationship and connection of all three has received limited research. The aim of this essay is to explore how they all relate to one another, to see what neural areas of involvement they have in common, and finally to see if there is a potential to administer oxytocin in order to alter empathy and/or depression. The sources used are published literature on the topics, found in for example Google Scholar and Worldcat. What was found was that both emotional and cognitive empathy have a positive relationship with oxytocin. Emotional empathy has in most research a positive relationship with depression while cognitive empathy seems to have a negative relationship with depression.Depression has a negative correlation with oxytocin. The neural areas of common involvement were amygdala, hippocampus, and cingulate cortex. Future research should look at how empathy, oxytocin, and depression affect each other, and why this happens. It is also important to look at the possibilities of affecting a neural area involved in empathy, oxytocin, and/or depression in order to make an impact on any of these factors.

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    The relationships of empathy, oxytocin, and depression
  • 144.
    Hamdi, Cassandra
    Högskolan i Skövde, Institutionen för biovetenskap.
    Clostridium difficile: Rapid typing Clostridium difficile using MALDI-TOF MS analysis2019Självständigt arbete på grundnivå (kandidatexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
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  • 145.
    Hammarberg, Maxine
    Högskolan i Skövde, Institutionen för biovetenskap.
    Kognitiv kontroll, självreglering och impulsivitet2019Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Kognitiv kontroll är förmågan att flexibelt anpassa sitt beteende till en eller flera specifika inre motiverande handlingar. Kognitiv kontroll möjliggör denna fokusering för de krav som informationsprocessen kräver. Kognitiv kontroll samt självreglering handlar bland annat om en så kallad top-down informationsprocess i ett globalt neuralt nätverk som pågår i den mänskliga hjärnan. Vi människor utövar denna kognitiva kontroll varje dag i vårat vardagliga liv utan vidare reflektioner. Detta sker genom flera informationsprocesser samtidigt och det är därför svårt att finna en enhetlig integrerad förklaring till de underliggande neurala mekanismerna. Syftet med arbetet är att förklara vad kognitiv kontroll, självreglering och impulsivitet innebär. Kopplingen mellan dessa två kognitiva kapaciteter föreskrivs i denna uppsats gällande de neurala mekanismerna och även kopplingen mellan kognitiv kontroll och självreglering i form av prestationer av både kontrollerade experiment och det vardagliga livet. Medan impulsivitet kopplat till kognitiv kontroll och självreglering är konsekvensen av när de neurala och kognitiva processerna brister i någon mening. Studier relaterat till kognitiv kontroll, inhibering och impulsbeteende använder sig bland annat av functional magnetic resonance imaging (fMRI) för att studera och undersöka detta kognitiva fenomen. Idag beskrivs impulsivitet samt bristande kontroll möjligen som ett maladaptivt beteende med hjälp av bland annat fMRI. Ytterligare fMRI studier har även visat på att kognitiv kontroll samt bristande kognitiv kontroll möjligen kan handla om en minskad eller ökad aktivering i nucleus accumbens, insulan och anterior cingulate cortex (ACC). Forskare inom ämnet har försökt att grundligt undersöka detta neurala nätverk genom flera olika perspektiv och därav presenterar uppsatsen några olika exempel av dessa ingångar för att möjliggöra ett brett perspektiv av denna komplexa mentala kapacitet. Resultaten inom ämnet visar än idag på en komplex multifaciterad natur av de underliggande neurala korrelaten.

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  • 146.
    Hammarsten Yder, Emma
    Högskolan i Skövde, Institutionen för biovetenskap.
    Sex Differences in Adolescent Depression2018Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [en]

    At the age of 13, the 2:1 ratio becomes evident. It entails the fact that after puberty, twice as many females as compared to males suffer from depressive episodes. Much research has been conducted to highlight key contributing factors that aid in the onset and the timing of the 2:1 ratio. Many researchers emphasize hormonal influences and the onset of puberty as key contributors, with theories such as the gonadic theory andthe interactional hypothesis both highlighting the role of hormones in the existence and the emergence of the 2:1 ratio during adolescence. Furthermore, a large variety of researchers emphasize females increased stress sensitivity and stress reactivity as key contributors to the 2:1 ratio. Critically, research concerning hormonal- and stress-related factors will be included. However, an additional focus will be on neurodevelopmental sex differences. This, as brain-based sex differences have been paid too little attention in theories and models concerning the emergence of the 2:1 ratio during adolescence. Results from research conducted to unravel the mystery of sex differences within the adolescent brain emphasize the impact of sex hormones on the maturational sexual differentiation occurring within the adolescent brain. It has been hypothesized that increases in female adolescent depression might occur in accordance with upsurges in peripheral estrogen levels, during puberty. This seems to suggest that there is an interaction between the effects of circulating ovarian hormones in relation to both sexual differentiation in brain organization and depression susceptibility. Hence, the point of this essay is to delineate key contributing factors that potentially govern the existence and onset of the 2:1 ratio during adolescence by emphasizing the areas of (a) sex-based neurodevelopmental factors, (b) hormonal factors and (c) stress-related factors.

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    Titel: Sex Differences in Adolescent Depression
  • 147.
    Handlin, Linda
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för vård och natur.
    Hydbring-Sandberg, Eva
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden .
    Nilsson, Anne
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, Skara, Sweden .
    Ejdebäck, Mikael
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Göteborgs universitet.
    Jansson, Anna
    Swedish Univ Agr Sci, Dept Anim Nutr & Management, S-75007 Uppsala, Sweden.
    Uvnäs-Moberg, Kerstin
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för vård och natur.
    Short-Term Interaction between Dogs and Their Owners: Effects on Oxytocin, Cortisol, Insulin and Heart Rate-An Exploratory Study2011Ingår i: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 24, nr 3, s. 301-315Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 148.
    Handlin, Linda
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Nilsson, Anne
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Ejdebäck, Mikael
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Hydbring-Sandberg, Eva
    University of Agricultural Sciences, Uppsala.
    Uvnäs-Moberg, Kerstin
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Associations between the Psychological Characteristics of the Human-Dog Relationship and Oxytocin and Cortisol Levels2012Ingår i: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 25, nr 2, s. 215-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 149.
    Hassan Abbas, Cattie
    Högskolan i Skövde, Institutionen för biovetenskap.
    Feeling Close to Someone: The Neural Correlates of Social Connection2019Självständigt arbete på grundnivå (kandidatexamen), 15 poäng / 22,5 hpStudentuppsats (Examensarbete)
    Abstract [en]

    During the course of human evolution, being a member of a group has been more beneficial for survival than being alone. Food gathering, protection from predators, cooperation, and care for offspring are distributed among group members, increasing the likelihood for survival. It is as if there is an interplay between agent and environment that interprets being socially cooperative as pleasurable and being left out as painful. Studies have been dedicated to examine how our social life is one of the most important aspects of health and well-being, particularly social relationships. Since this link has been demonstrated, it would be interesting to incorporate the field of neuroscience to understand the involvement of the human brain in our social experiences, specifically the experience of social connection. The current state of neuroscience does not allow researchers to examine this kind of subjective experiences, simply because of the lack of proper tools and knowledge. Research in this field has come a long way since the early stages, and studies have indicated on significant results regarding the involved neural regions. The dorsal anterior cingulate cortex (dACC) and the anterior insula (AI) are active when threats to social connection is experienced. They are also active in situations were survival is threatened. An experience of social connection evokes a feeling of (social) safety, in part because it activates regions of the brain associated with physical safety, such as the ventromedial prefrontal cortex (VMPFC). In similar fashion, a sense of social closeness ("warmth") activates the ventral striatum (VS), which is associated with physical warmth and studies have shown that social and physical warmth share overlapping neural activity in VS. Finally, Mu-opioids have been shown to be responsible for social bonding; while using an opioid antagonist such as naltrexone, decreases the feeling of social connection. Studies in this field are few; one should take their results with caution. The field continues to grow, and the studies that have been done to date give exciting hints of the influence of social relationships on physical health and mental well-being.

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  • 150.
    Hedberg Oldfors, Carola
    et al.
    Sahlgrenska Academy, University of Gothenburg.
    Garcia Dios, Diego
    Sahlgrenska Academy, University of Gothenburg.
    Linder, Anna
    Sahlgrenska Academy, University of Gothenburg.
    Visuttijai, Kittichate
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Sahlgrenska Academy, University of Gothenburg.
    Samuelson, Emma
    Sahlgrenska Academy, University of Gothenburg.
    Karlsson, Sandra
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Nilsson, Staffan
    Chalmers University of Technology.
    Behboudi, Afrouz
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Analysis of an independent tumor suppressor locus telomeric to Tp53 suggested Inpp5k and Myo1c as novel tumor suppressor gene candidates in this region2015Ingår i: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 16, nr 1, artikel-id 80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

    RESULTS:

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

    CONCLUSION:

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

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