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  • 501.
    Tanner Wärme, Evelina
    University of Skövde, School of Bioscience.
    Vedlevande skalbaggars förekomst i förhållande till olika typer av död ved2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 502.
    Temnerud, Lars
    University of Skövde, School of Bioscience. lars.temnerud@gmail.com.
    The key role of dopamine as the neural correlate of intrinsic motivation and trait plasticity2018Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Self-determination theory (SDT), a motivation theory, consists of motivation types: intrinsic motivation, extrinsic motivation, and amotivation, where the social environment is important. SDT’s motivation orientations are about individual differences in people’s tendencies to orient towards environments. The five factor model (FFM), a personality theory, consists of five factors and can be grouped into two metatraits; plasticity: extraversion and openness; and stability: agreeableness, conscientiousness, and neuroticism. Studies show that SDT’s motivation orientations and the factors of FFM significantly covary. Intrinsic motivation and trait plasticity have similar features; the desire for exploration, engagement, well-being, and dopamine as neural correlate. The thesis reviews the role of dopamine as the neural correlate of intrinsic motivation and trait plasticity – a relation between motivation and personality. Dopamine and trait plasticity function to attain rewards of uncertainty and explore, but uncertainty is threatening. Salience coding neurons, value coding neurons and a combination of both are related, respectively, to rewards of information, specific rewards and the value of any uncertainty. Intrinsic motivation is related to the value coding neurons, flow via D2 receptors, the salience network, and the seeking system. Conclusions: there are many appealing similarities and rational that relate constructs/mechanisms – motivation is related to personality; can there even be a common construct? However; results based on proposed theories, neuroscientific quality issues, early inconsistent findings of intrinsic motivation mechanisms, and trait stability are speculated to, also, be needed to model intrinsic motivation. Unifying cross-disciplinary work and proposed theories of neural correlates are encouraged.

  • 503.
    Thelander, Jenny
    University of Skövde, School of Bioscience.
    Neural Mechanisms Underlying Self-Localization in Rodents2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The ability to self-localize and navigate in both stable and changing environments is crucial for the survival of many species. Research conducted on the non-human mammalian hippocampus and surrounding brain structures has uncovered several classes of spatial related cells. These cells provide the rest of the brain with knowledge of the animal’s location and direction—knowledge that is subsequently used in spatial navigation. This thesis provides an overview of three types of cells underlying this ability in rodents. First, place cells located in the hippocampus encode the animal’s specific location in the environment. Second, head direction cells found throughout the Papez circuit convey the angular direction of the animal’s head. Last, grid cells in the medial entorhinal cortex generate a regular triangular grid spanning the entire explored setting. The focus of this review lies on the most salient features of these types of cells. It is also considered how the cells respond to manipulations of external and internal information, as well as how different lesions affect their activity. 

  • 504.
    Theodoropoulou, Eleftheria
    University of Skövde, School of Bioscience.
    DNA METHYLATION AGE ACCELERATION IN MULTIPLE SCLEROSIS2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Age acceleration is a measure indicating if a tissue is aging at an expected rate or not. In this study,the epigenetic clock was used to calculate age acceleration based on DNA methylation values inMultiple Sclerosis datasets. The samples were of whole blood, purified blood cell types and neuronsand included individuals with the disease, as well as controls. Various factors were explored for theireffect on the age acceleration in the context of the disease. In addition, three different normalisationoptions (no normalisation, Noob and Funnorm normalisation) were compared in order to assess theireffect on the output of the epigenetic clock algorithm. Finally, a workflow was proposed for theepigenetic clock analysis, highlighting suitable methods for processing, analysing statistically andvisualising the data.

  • 505.
    Thulin Nilsson, Linnea
    University of Skövde, School of Bioscience.
    The Role of Primary Visual Cortex in Visual Awareness2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Despite its great complexity, a great deal is known about the organization and information-processing properties of the visual system. However, the neural correlates of visual awareness are not yet understood. By studying patients with blindsight, the primary visual cortex (V1) has attracted a lot of attention recently. Although this brain area appears to be important for visual awareness, its exact role is still a matter of debate. Interactive models propose a direct role for V1 in generating visual awareness through recurrent processing. Hierarchal models instead propose that awareness is generated in later visual areas and that the role of V1 is limited to transmitting the necessary information to these areas. Interactive and hierarchical models make different predictions and the aim of this thesis is to review the evidence from lesions, perceptual suppression, and transcranial magnetic stimulation (TMS), along with data from internally generated visual awareness in dreams, hallucinations and imagery, this in order to see whether current evidence favor one type of model over the other. A review of the evidence suggests that feedback projections to V1 appear to be important in most cases for visual awareness to arise but it can arise even when V1 is absent. 

  • 506.
    Thyberg, Joel
    University of Skövde, School of Bioscience.
    Dehumanization in the brain2019Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Dehumanization is a process whereby people fail to view others as human beings. Instead, the others are perceived as nonhuman animals or objects, unworthy of the same moral treatment. Dehumanization has previously been studied in a variety of different scholarly domains without adhering to a uniform theoretical framework. This literature review contrasts research on fully humanized perception, with research on dehumanized perception, and proposes neural areas which are likely to be involved. Not every aspect of dehumanization can be understood at the neurological level. To understand what factors lead up to, and modulates dehumanization, other perspectives might also be necessary. Dehumanized perception is coupled with reduced activity in the social cognitive brain network, a wide network which encompasses several cortical and subcortical areas. This disengages prosocial abilities and allows for other people to be treated like objects and means to an end. One area of special interest is the medial prefrontal cortex (MPFC). It functions as an integration center in the person perception network and is also active when we make moral judgments, empathize, or take the perspective of someone else. For this reason, the MPFC is sometimes used as an index of dehumanized perception.

  • 507.
    Tiainen Losno, Emily Angela
    University of Skövde, School of Bioscience. Karolinska Institutet .
    MED13 regulates substrate utilization and bioenergetics in human skeletal muscle2018Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Mediator Complex has an essential function in regulating the transcription of several genes, working as a scaffold between transcription factors and polymerase II. It is composed of 26 subunits, with the kinase, or CDK subunit, being one of the most important for the mediator complex activation. In fact, when the kinase subunit is bound to the complex, binding between the mediator complex and polymerase II is hindered and therefore transcription is repressed. This suggests that the kinase complex and its components are essential for the expression of polymerase II transcripts. MED13 is part of the kinase subunit and high-throughput transcriptomic analysis showed MED13 as being upregulated in human skeletal muscle biopsies following an oral glucose tolerance test.

    The aim of this project is to understand the function of MED13 in human skeletal muscle metabolism and the relationship between MED13 knockdown and AMPK (AMP-activated protein kinase) function. Primary human skeletal muscles cells obtained from three healthy donors were cultured and transfection with MED13 siRNA was performed on differentiated myotubes. Metabolic assays such as fatty acid and glucose oxidation were performed as well as mitochondrial function. Quantitative PCR and western blot techniques were used to assess the pathways altered by MED13.

    Glucose uptake and fatty acid transporters were significantly increased upon MED13 silencing. Reduction in fatty acid oxidation and unchanged glucose oxidation suggest that MED13 favors substrate storage. Western blot analysis hinted on an increase in AMPK phosphorylation and in mitochondrial biogenesis. The production of ATP by mitochondria was also increased. In conclusion, MED13 plays an important role in human skeletal muscle substrate utilization for energy production.

     

  • 508.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, article id 31234Article in journal (Refereed)
    Abstract [en]

    Background: The increasing prevalence of penicillin non-susceptible pneumococci (PNSP) throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting.

    Methods: An individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden). A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed.

    Results: Model simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year), the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community.

    Conclusion: The frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

  • 509.
    Tilevik, Diana
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital , Skövde, Sweden.
    Clinical routine biomarkers in combination for early identification of patients with bacterial sepsis2019Conference paper (Refereed)
  • 510.
    Tilevik, Diana
    et al.
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Saxenborn, Patricia
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Fagerlind, Magnus
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Lubovac-Pilav, Zelmina
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, Systems Biology Research Environment.
    Enroth, Helena
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Using next-generation sequencing to study biodiversity in Klebsiella spp. isolated from patients with suspected sepsis2019Conference paper (Refereed)
  • 511.
    Torberger, Fredrik
    University of Skövde, School of Bioscience.
    MIND-WANDERING – A Human Condition2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Mind-wandering was until recently not a mainstream topic of research. The aim of this literature review is to present current views on the definition of mind-wandering and how the phenomenon is experienced. Furthermore, it gives an account of the implications of mind-wandering on cognitive performance, as well as its neurological correlates. In addition, the methods used to study mind-wandering are reviewed.The study of mind-wandering reveals a highly frequent phenomenon with practical consequences on a broad scale, both disruptive and supportive to goal-related behaviour and wellbeing in general. Originating from the default network, and its regions related to representations of self, memory, Theory of Mind, empathy and creativity, mind-wandering is hypothesized to be a function for planning one’s future life. Suggested further research concerns how mind-wandering can be countered, detected from the outside and whether it alters the physical feature of the brain.

  • 512.
    Torra, Vicenç
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Jonsson, Annie
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Navarro‐Arribas, Guillermo
    Universitat Autònoma de Barcelona, Spain / Center for Cybersecurity Research of Catalonia (CYBERCAT), Spain.
    Salas, Julián
    Center for Cybersecurity Research of Catalonia (CYBERCAT), Spain / Universitat Oberta de Catalunya (UOC), Barcelona, Spain.
    Synthetic generation of spatial graphs2018In: International Journal of Intelligent Systems, ISSN 0884-8173, E-ISSN 1098-111X, Vol. 32, no 12, p. 2364-2378Article in journal (Refereed)
    Abstract [en]

    Graphs can be used to model many different types of interaction networks, for example, online social networks or animal transport networks. Several algorithms have thus been introduced to build graphs according to some predefined conditions. In this paper, we present an algorithm that generates spatial graphs with a given degree sequence. In spatial graphs, nodes are located in a space equiped with a metric. Our goal is to define a graph in such a way that the nodes and edges are positioned according to an underlying metric. More particularly, we have constructed a greedy algorithm that generates nodes proportional to an underlying probability distribution from the spatial structure, and then generates edges inversely proportional to the Euclidean distance between nodes. The algorithm first generates a graph that can be a multigraph, and then corrects multiedges. Our motivation is in data privacy for social networks, where a key problem is the ability to build synthetic graphs. These graphs need to satisfy a set of required properties (e.g., the degrees of the nodes) but also be realistic, and thus, nodes (individuals) should be located according to a spatial structure and connections should be added taking into account nearness.

  • 513.
    Torra, Vicenç
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Karlsson, Alexander
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Steinhauer, H. Joe
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Berglund, Stefan
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Artificial Intelligence2019In: Data Science in Practice / [ed] Alan Said, Vicenç Torra, Springer, 2019, p. 9-26Chapter in book (Refereed)
    Abstract [en]

    This chapter gives a brief introduction to what artificial intelligence is. We begin discussing some of the alternative definitions for artificial intelligence and introduce the four major areas of the field. Then, in subsequent sections we present these areas. They are problem solving and search, knowledge representation and knowledge-based systems, machine learning, and distributed artificial intelligence. The chapter follows with a discussion on some ethical dilemma we find in relation to artificial intelligence. A summary closes this chapter.

  • 514.
    Toräng, Per
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience. Department of Plant Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Vikström, Linus
    Department of Plant Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Wunder, Jörg
    Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Cologne, Germany.
    Wötzel, Stefan
    Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Cologne, Germany.
    Coupland, George
    Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Cologne, Germany.
    Ågren, Jon
    Department of Plant Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
    Evolution of the selfing syndrome: Anther orientation and herkogamy together determine reproductive assurance in a self-compatible plant2017In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 9, p. 2206-2218Article in journal (Refereed)
    Abstract [en]

    Capacity for autonomous self-fertilization provides reproductive assurance, has evolved repeatedly in the plant kingdom, and typically involves several changes in flower morphology and development (the selfing syndrome). Yet, the relative importance of different traits and trait combinations for efficient selfing and reproductive success in pollinator-poor environments is poorly known. In a series of experiments, we tested the importance of anther-stigma distance and the less studied trait anther orientation for efficiency of selfing in the perennial herb Arabis alpina. Variation in flower morphology among eight self-compatible European populations was correlated with efficiency of self-pollination and with pollen limitation in a common-garden experiment. To examine whether anther-stigma distance and anther orientation are subject to directional and/or correlational selection, and whether this is because these traits affect pollination success, we planted a segregating F2 population at two native field sites. Selection strongly favored a combination of introrse anthers and reduced anther-stigma distance at a site where pollinator activity was low, and supplemental hand-pollination demonstrated that this was largely because of their effect on securing self-pollination. The results suggest that concurrent shifts in more than one trait can be crucial for the evolution of efficient self-pollination and reproductive assurance in pollinator-poor habitats.

  • 515.
    Toto, Robert D.
    et al.
    University of Texas Southwestern Medical Center, Dallas, TX, USA.
    Goldenberg, Ronald
    LMC Diabetes & Endocrinology, Thornhill, ON, Canada.
    Chertow, Glenn M.
    Stanford University School of Medicine, CA, USA.
    Cain, Valerie
    Bogier Clinical and IT Solutions, Raleigh, NC, USA.
    Stefánsson, Bergur V.
    Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Sjöström, Carl David
    Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Correction of hypomagnesemia by dapagliflozin in patients with type 2 diabetes: A post hoc analysis of 10 randomized, placebo-controlled trials2019In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 33, no 10, article id 107402Article in journal (Refereed)
    Abstract [en]

    Aims: Hypomagnesemia (serum magnesium [Mg] <0.74 mmol/L [<1.8 mg/dL]) is commonly observed in patients with type 2 diabetes (T2D). This study investigated the effect of treatment with dapagliflozin 10 mg on Mg concentrations in patients with T2D. Methods: In this post hoc analysis, we used pooled data from 10 placebo-controlled studies of dapagliflozin over 24 weeks of treatment in patients with T2D. We evaluated the change in Mg in patients receiving dapagliflozin vs. placebo overall, and in subgroups with baseline hypomagnesemia and normal/hypermagnesemia (≥0.74 mmol/L [≥1.8 mg/dL]). We determined the proportion of patients with baseline hypomagnesemia who achieved Mg ≥0.74 mmol/L (≥1.8 mg/dL). Results: A total of 4398 patients with T2D were included. The mean change from baseline to week 24 in Mg was significantly larger with dapagliflozin vs. placebo; difference, 0.06 mmol/L (95% confidence interval [CI]: 0.05, 0.06). The proportion of patients with Mg within the population reference range after 24 weeks of treatment was significantly higher with dapagliflozin vs. placebo; difference, 47.8% (95% CI: 41.4, 53.9). The proportion of patients displaying hypermagnesemia did not increase with dapagliflozin treatment. Conclusions: Treatment with dapagliflozin 10 mg resulted in correction of Mg concentrations in patients with T2D and hypomagnesemia. 

  • 516.
    Tuominen, Jarno
    et al.
    Department of Psychology and Speech-Language Pathology, University of Turku, Finland.
    Peltola, Karoliina
    Department of Psychology and Speech-Language Pathology, University of Turku, Finland.
    Saaresranta, Tarja
    Division of Medicine, Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland / Sleep Research Centre, Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Turku, Finland /Turku Brain and Mind Center, University of Turku, Turku, Finland.
    Sleep Parameter Assessment Accuracy of a Consumer Home Sleep Monitoring Ballistocardiograph Beddit Sleep Tracker: A Validation Study2019In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 15, no 3, p. 483-487, article id PII jc-18-00561Article in journal (Refereed)
    Abstract [en]

    Study Objectives: Growing interest in monitoring sleep and well-being has created a market for consumer home sleep monitoring devices. Additionally, sleep disorder diagnostics, and sleep and dream research would benefit from reliable and valid home sleep monitoring devices. Yet, majority of currently available home sleep monitoring devices lack validation. In this study, the sleep parameter assessment accuracy of Beddit Sleep Tracker (BST), an unobtrusive and non-wearable sleep monitoring device based on ballistocardiography, was evaluated by comparing it with polysomnography (PSG) measures. We measured total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE). Additionally, we examined whether BST can differentiate sleep stages. Methods: We performed sleep studies simultaneously with PSG and BST in ten healthy young adults (5 female/5 male) during two non-consecutive nights in a sleep laboratory. Results: BST was able to distinguish SOL with some accuracy. However, it underestimated WASO and thus overestimated TST and SE. Also, it failed to discriminate between non-rapid eye movement sleep stages and did not detect the rapid eye movement sleep stage. Conclusions: These findings indicate that BST is not a valid device to monitor sleep. Consumers should be careful in interpreting the conclusions on sleep quality and efficiency provided by the device.

  • 517.
    Tuominen, Jarno
    et al.
    Department of Psychology, University of Turku, Finland / Turku Brain and Mind Center, University of Turku, Finland.
    Stenberg, Tuula
    Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland / Turku Brain and Mind Center, University of Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology, University of Turku, Finland / Turku Brain and Mind Center, University of Turku, Finland.
    Social contents in dreams: An empirical test of the Social Simulation Theory2019In: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 69, p. 133-145Article in journal (Refereed)
    Abstract [en]

    Social Simulation Theory (SST) considers the function of dreaming to be the simulation of social events. The Sociality Bias and the Strengthening hypotheses of SST were tested. Social Content Scale (SCS) was developed to quantify social events. Additionally, we attempted to replicate a previous finding (McNamara et al., 2005, Psychological Science) of REM dreams as predisposed to aggressive, and NREM dreams to prosocial interactions. Further, we investigated the frequency and quality of interactions in late vs early REM and NREM dreams. Data consisted of wake, REM and NREM home dream reports (N = 232, 116, 116, respectively) from 15 students. Dreams overrepresented social events compared to wake reports, supporting the Sociality Bias hypothesis. However, the Strengthening Hypothesis was not supported. We weren't able to replicate the McNamara et al. finding, and no time of night effect was found. While SST gained partial support, further research on social contents in dreams is required. © 2019 Elsevier Inc.

  • 518.
    Udayangani, Akwaththage
    University of Skövde, School of Bioscience.
    Facial age and anger expression: An event-related brain potential study2019Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The perception of human faces is affected by different facial features. For example, older faces are processed differently to younger ones and faces expressing diverse emotions are also processed differently. Research shows that angry faces are more attended to compared to neutral or other expressive faces, which is known as the ‘threat advantage’. This is evidenced by research on the late positive potential (LPP). The LPP is an event-related potential (ERP) component associated with affective processing, which seems to strongly respond to threats. The literature has indicated that older faces can elicit larger LPPs compared to young and neutral faces, and the LPP is more sensitive to emotional faces. The current experiment investigated subjective ratings in addition to the LPP in response to neutral and angry faces of young and old individuals, to examine how facial age influences the perception of anger. In a facial rating task, both the young and the old angry faces were rated as threatening faces, while old neutral faces were indicated to be more threatening than young neutral faces. Similarly, participants had a higher LPP for old angry faces. This data, in combination, suggests a higher emotional salience of old angry faces compared to either young angry or (young or old) neutral faces.

  • 519.
    Ulfenborg, Benjamin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Bioinformatics tools for discovery and evaluation of biomarkers: Applications in clinical assessment of cancer2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cancer is a disease characterized by abnormal proliferation of cells in the body and ranks as the second leading cause of death worldwide. In order to improve cancer patient care, a major focus of cancer research is to discover biomarkers. A biomarker is a biological molecule found in tissues or body fluids and can be used to predict or assess disease states. The aim of this thesis is to develop bioinformatics tools for discovery and evaluation of novel biomarkers from high-throughput datasets.

    MicroRNAs (miRNAs) are short non-coding RNAs that function as negative regulators of gene expression. Dysregulation of miRNAs in cancer is frequently reported, making them interesting as biomarker candidates. GenoScan was developed for genome-wide discovery of miRNA-coding genes, as a first step in the identification of novel mi-RNA biomarkers.

    High-throughput technologies such as microarrays allow researchers to measure the expression of thousands of genes or miRNAs simultaneously. The Decision Trunk Classifier (DTC) algorithm has been developed to screen datasets from these experiments for biomarker candidates. When applied to a miRNA expression dataset for endometrial cancer (EC) samples vs. controls, a two-marker model with 98 % accuracy was generated. These miRNAs (hsa-miR-183-5p and hsa-miRPlus-C1070) are promising as biomarkers for EC screening.

    The miREC database was developed to store gene and miRNA data from curated expression profiling studies of EC, as well as gene-miRNA regulatory connections. Using gene-miRNA interaction networks from miREC, the roles of miRNAs in cancer hallmark acquisition can be clarified. To further support exploratory analysis of expression data, DTC was extended with partial least squares regression models. The resulting PLS-DTC algorithm can be used to gain deeper insights into the perturbation of biological processes and pathways.

  • 520.
    Ulfenborg, Benjamin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Vertical and horizontal integration of multi-omics data with miodin2019In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 20, no 649Article in journal (Refereed)
    Abstract [en]

    Background: Studies on multiple modalities of omics data such as transcriptomics, genomics and proteomics are growing in popularity, since they allow us to investigate complex mechanisms across molecular layers. It is widely recognized that integrative omics analysis holds the promise to unlock novel and actionable biological insights into health and disease. Integration of multi-omics data remains challenging, however, and requires combination of several software tools and extensive technical expertise to account for the properties of heterogeneous data.

    Results: This paper presents the miodin R package, which provides a streamlined workflow-based syntax for multi-omics data analysis. The package allows users to perform analysis of omics data either across experiments on the same samples (vertical integration), or across studies on the same variables (horizontal integration). Workflows have been designed to promote transparent data analysis and reduce the technical expertise required to perform low-level data import and processing.

    Conclusions: The miodin package is implemented in R and is freely available for use and extension under the GPL-3 license. Package source, reference documentation and user manual are available at https://gitlab.com/algoromics/miodin.

  • 521.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jurcevic, Sanja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Lindelöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    miREC: a database of miRNAs involved in the development of endometrial cancer2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, no 1, article id 104Article in journal (Refereed)
    Abstract [en]

    Background

    Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth most common cancer diagnosis overall among women. As with many other forms of cancer, it has been shown that certain miRNAs are differentially expressed in EC and these miRNAs are believed to play important roles as regulators of processes involved in the development of the disease. With the rapidly growing number of studies of miRNA expression in EC, there is a need to organize the data, combine the findings from experimental studies of EC with information from various miRNA databases, and make the integrated information easily accessible for the EC research community.

    Findings

    The miREC database is an organized collection of data and information about miRNAs shown to be differentially expressed in EC. The database can be used to map connections between miRNAs and their target genes in order to identify specific miRNAs that are potentially important for the development of EC. The aim of the miREC database is to integrate all available information about miRNAs and target genes involved in the development of endometrial cancer, and to provide a comprehensive, up-to-date, and easily accessible source of knowledge regarding the role of miRNAs in the development of EC. Database URL: http://www.mirecdb.orgwebcite.

    Conclusions

    Several databases have been published that store information about all miRNA targets that have been predicted or experimentally verified to date. It would be a time-consuming task to navigate between these different data sources and literature to gather information about a specific disease, such as endometrial cancer. The miREC database is a specialized data repository that, in addition to miRNA target information, keeps track of the differential expression of genes and miRNAs potentially involved in endometrial cancer development. By providing flexible search functions it becomes easy to search for EC-associated genes and miRNAs from different starting points, such as differential expression and genomic loci (based on genomic aberrations).

  • 522.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Karlsson, Alexander
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Riveiro, Maria
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Améen, Caroline
    Takara Bio Europe AB, Gothenburg, Sweden.
    Åkesson, Karolina
    Takara Bio Europe AB, Gothenburg, Sweden.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Cardiovascular and Metabolic Disease Global Medicines Development Unit, AstraZeneca, Mölndal, Sweden.
    Synnergren, Jane
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179613Article in journal (Refereed)
    Abstract [en]

    The development of high-throughput biomolecular technologies has resulted in generation of vast omics data at an unprecedented rate. This is transforming biomedical research into a big data discipline, where the main challenges relate to the analysis and interpretation of data into new biological knowledge. The aim of this study was to develop a framework for biomedical big data analytics, and apply it for analyzing transcriptomics time series data from early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. To this end, transcriptome profiling by microarray was performed on differentiating human pluripotent stem cells sampled at eleven consecutive days. The gene expression data was analyzed using the five-stage analysis framework proposed in this study, including data preparation, exploratory data analysis, confirmatory analysis, biological knowledge discovery, and visualization of the results. Clustering analysis revealed several distinct expression profiles during differentiation. Genes with an early transient response were strongly related to embryonic-and mesendoderm development, for example CER1 and NODAL. Pluripotency genes, such as NANOG and SOX2, exhibited substantial downregulation shortly after onset of differentiation. Rapid induction of genes related to metal ion response, cardiac tissue development, and muscle contraction were observed around day five and six. Several transcription factors were identified as potential regulators of these processes, e.g. POU1F1, TCF4 and TBP for muscle contraction genes. Pathway analysis revealed temporal activity of several signaling pathways, for example the inhibition of WNT signaling on day 2 and its reactivation on day 4. This study provides a comprehensive characterization of biological events and key regulators of the early differentiation of human pluripotent stem cells towards the mesoderm and cardiac lineages. The proposed analysis framework can be used to structure data analysis in future research, both in stem cell differentiation, and more generally, in biomedical big data analytics.

  • 523.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Informatics Research Centre.
    Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression2015In: International Journal of Data Mining and Bioinformatics, ISSN 1748-5681, Vol. 13, no 4, p. 338-359Article in journal (Refereed)
    Abstract [en]

    In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods. In addition, the sequence-folding step is addressed by investigating the impact of secondary structure prediction methods and the choice of input sequence length on prediction performance. Both the accuracy of secondary structure predictions and the miRNA prediction are evaluated. In the benchmark of hairpin classification methods, the regression model achieved highest classification accuracy. Of the structure prediction methods evaluated, ContextFold achieved the highest agreement between predicted and experimentally determined structures. However, both the choice of secondary structure prediction method and input sequence length had limited impact on hairpin classification performance.

  • 524.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Klinga-Levan, Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    GenoScan: Genomic Scanner for Putative miRNA Precursors2014In: Bioinformatics Research and Applications: 10th International Symposium, ISBRA 2014, Zhangjiajie, China, June 28-30, 2014. Proceedings / [ed] Mitra Basu, Yi Pan, Jianxin Wang, Springer, 2014, p. 266-277Conference paper (Refereed)
    Abstract [en]

    The significance of miRNAs has been clarified over the last decade as thousands of these small non-coding RNAs have been found in a wide variety of species. By binding to specific target mRNAs, miRNAs act as negative regulators of gene expression in many different biological processes. Computational approaches for discovery of miRNAs in genomes usually take the form of an algorithm that scans sequences for miRNA-characteristic hairpins, followed by classification of those hairpins as miRNAs or nonmiRNAs. In this study, two new approaches to genome-scale miRNA discovery are presented and evaluated. These methods, one ensemble-based and one using logistic regression, have been designed to detect miRNA candidates without relying on conservation or transcriptome data, and to achieve high-confidence predictions in reasonable computational time. GenoScan achieves high accuracy with a good balance between sensitivity and specificity. In a benchmark evaluation including 15 previously published methods, the regression-based approach in GenoScan achieved the highest classification accuracy.

  • 525.
    Ullah, Naseem
    University of Skövde, School of Bioscience.
    Disease modules identification in heterogenous diseases with WGCNA method2019Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The widely collected and analyzed genetic data help in understanding the underlying mechanisms of heterogeneous diseases. Cellular components interact in a network fashion where genes are nodes and edges are the interactions. The failure in individual genes lead to dys-regulation of sub-groups of genes which causes a disease phenotype, and this dys-functional region is called a disease module. Disease module identification in complex diseases such as asthma and cancer is a huge challenge. Despite the development of numerous sophisticated methods there is a still no gold standard. In this study we apply different parameter settings to test the performance of a widely used method for disease module detection in multi-omics data called Weighted Gene Co-expression Network Analysis (WGCNA). A systematic approach is used to identify disease modules in asthma and arthritis diseases. The accuracy of obtained modules is validated by a pathway scoring algorithm (PASCAL) and GWAS SNP enrichment. Our results differ between the tested data sets and therefore we cannot conclude with recommendations for an optimal setting that could perform best for multiple data sets using this method.

  • 526.
    Vallabhu, Rishu
    et al.
    University of Skövde.
    Falck, Eva
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Lindlöf, Angelica
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    A systems biology view of the spliceosome component Phf5a in relation to estrogen and cancer2014In: Journal of Computer Science and Systems Biology, ISSN 0974-7230, Vol. 7, no 6, p. 193-202Article in journal (Refereed)
    Abstract [en]

    Cancer is a broad term for a wide spectrum of diseases and which involves the alteration in expression levels of several hundreds of genes. As such, the study of the disease from a systems biology point of view becomes rational, as the properties of a system as a whole may be very different from the properties of its individual components. However, understanding a network at the systems level not only requires knowledge about the components of the network, but also the interactions between them.

    Here, a systems biology view of the rat PHD finger protein 5A (Phf5a) gene was attempted; a gene previously identified as aberrantly expressed in estrogen dependent endometrial adenocarcinoma tumors from both rat and human. Phf5 ais a highly conserved cysteine rich (C4HC3) zinc finger and such proteins predominantly have a role in chromatin mediated transcriptional regulation. Moreover, PHF5A is a component of the macromolecular complex spliceosome that takes part in pre-mRNA splicing and spliceosome component coding genes have previously been shown to be implicated in various cancer types and suggested to potentially be novel antitumor drugs.

    To derive a systems biology view, in this study, a weighted gene network was inferred from a list of genes having correlated expression profiles to Phf5a as nodes, and common transcription factors and microRNAs regulating these genes together with annotation about biological process ontology term(s) and pathway(s) as edge weights. In the inferred network a higher weight indicates more annotation shared between two genes and, hence, the network facilitates the identification of closely interacting genes with Phf5a. The results show that highly weighted edges connect Phf5a to other spliceosome components, but also to genes involved in the metabolism of proteins, proteasome and DNA replication, repair and recombination. The results also link Phf5a to the Myc/Rb/E2F pathway, one of the central pathways associated with cancer. The proposed method for inferring a weighted gene network can easily be applied to other genes and diseases. 

  • 527.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Dreams2016In: The SAGE Encyclopedia of Theory in Psychology / [ed] Harold L. Miller, Thousand Oaks: Sage Publications, 2016Chapter in book (Other academic)
  • 528.
    Valli, Katja
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland.
    Frauscher, Birgit
    Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
    Peltomaa, Taina
    Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland.
    Gschliesser, Viola
    Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland.
    Högl, Birgit
    Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
    Dreaming furiously?: A sleep laboratory study on the dream content of people with Parkinson's disease and with or without rapid eye movement sleep behavior disorder2015In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 16, no 3, p. 419-427Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) has been related to altered, action-filled, vivid, and aggressive dream content, but research comparing the possible differences in dreams of Parkinson's disease (PD) patients with and without RBD is scarce. The dream content of PD patients with and without RBD was analyzed with specific focus on action-filledness, vividness, emotional valence, and threats.

    METHODS: A total of 69 REM and NREM dream reports were collected in the sleep laboratory, 37 from nine PD patients with RBD and 32 from six PD patients without RBD. A content analysis of (1) action-filledness (actions and environmental events); (2) vividness (emotions and cognitive activity); (3) intensity of actions, events and emotions; (4) emotional valence, and (5) threatening events was performed on the transcripts.

    RESULTS: Altogether 563 dream elements expressing action-filledness and vividness were found. There were no significant between-group differences in the number or distribution of elements reflecting action-filledness or vividness, emotional valence or threats. In within-group analyses, PD patients with RBD had significantly more negative compared to positive dreams (p = 0.012) and compared to PD patients without RBD, a tendency to have more intense actions in their dreams (p = 0.066).

    CONCLUSIONS: Based on the results of this study, there are no major between-group differences in the action-filledness, vividness, or threat content of dreams of PD patients with and without RBD. However, within-group analyses revealed that dreams were more often negatively than positively toned in PD patients with RBD.

  • 529.
    Vestin, Amanda
    University of Skövde, School of Bioscience.
    Is There a You in Your Brain?: The Neuroscientific Support for the Bundle-Theory View of the Nature of the Self2019Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Why do you experience yourself as a continuous self? This is a central question when regarding the self and it has two kinds of answers: either there is something like an ego inside you which is the entity perceiving all your experiences (the ego theory-view), or there is no such thing as a self or an ego and you are just a collection of different perceptions (the bundle theory-view). There are many different components all contributing to the concept of self as a whole leading to different neuroscientific ways of measuring it and some researchers are arguing for the nonexistence of a unified self-system within the brain. The aim of this thesis is to review how neuroscientific findings might contribute to the philosophical debate about the nature of self. The thesis starts off by reviewing the different concepts and components with which the self is typically described, both in philosophy and in the empirical research field of neuroscience. Then follows a presentation of three important aspects of self-awareness – first-person perspective, self-reflection, and interoception – and their specific associated brain areas (namely, the medial prefrontal cortex, the posterior and anterior cingulate cortices, and insula). The purpose here is to examine how the self is approached in these studies. After this the thesis explores to what extent neuroscience supports the bundle theory-view, with a focus on reviewing the different brain networks involved in the processing of self. In conclusion, the thesis suggests that the literature reviewed provides neuroscientific support for the bundle theory-view that there is no unified self located in the brain, mostly because of the dissimilar neural activations associated with different self-related processes. In other words, the bundle theory seems to be correct despite the experienced feeling you have of being a continuous and unified self. 

  • 530.
    Vidlund, Elin
    University of Skövde, School of Bioscience.
    Moral cognition and its neural correlates: Possibilites for enhancement of moral cognition and behavior2018Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    This essay aims to provide an overview of some key theories and frameworks regarding moral cognition and its neural correlates, in order to examine the possibilities of enhancement of moral cognition. Moral cognition arises from the functional integration of several distinct brain regions and networks. These neural systems correspond to different socioaffective abilities, such as empathy and compassion, as well as sociocognitive abilities, such as theory of mind. Due to this neural distinction, these moral abilities, behaviors, and emotions can be targeted and trained separately. Recent research suggests that training sociocognitive and socioaffective abilities increases cortical thickness in corresponding brain regions and networks, hence providing support for adult neural plasticity in relation to moral cognition. Increased cortical thickness also corresponds to enhanced performance in socioaffective and sociocognitive abilities. Training compassion and empathy induce enhanced abilities to pick up emotional cues, as well as strengthen the motivation to alleviate others’ distress. Practicing theory of mind allows for a better understanding of the perspective of others, which has been indicated to reduce biases between individuals or societal groups. Thus, enhanced moral cognition can contribute to an increase in consideration for those affected by our choices and behavior, which may yield more compassionate, just, and safe societies.

  • 531.
    Viking, Jenny
    University of Skövde, School of Bioscience.
    Stress: Kognitiv Påverkan och Åtgärder för Återhämtning2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Stress är i sig inte farlig om den inte blir långvarig och konstant, den här rapporten har tittat på vilka effekter och eventuella konsekvenser stress har på de fysiologiska och kognitiva systemen hos människan. En långvarig aktivering av HPA-axeln, vilken kan kallas prestations/stressaxeln, leder bland annat till kroniskt förhöjda kortisolnivåer vilket har negativa effekter för hälsan. Strukturer i hjärnan vilka ofta kopplas till stressrelaterade sjukdomar är hippocampus och prefrontala kortex. De konsekvenserna som kan följa på långvarig stress är kognitiva nedsättningar och skador på bland annat hippocampus, brister i immunförsvaret, hjärt- och kärlsjukdomar, ångest, kroniskt utmattningssyndrom, mag- och tarmbesvär samt depression. I rapporten visas att stress har stora negativa konsekvenser på individnivå både gällande kognitiva funktioner, så som minne, och även på det fysiologiska systemet. Det finns åtgärder att använda för att reducera upplevelsen av stress samt de negativa effekterna av stress, så som fysisk aktivitet, mindfulness meditation och muskulär avslappning. 

  • 532.
    Virta, Maarit
    et al.
    University of Helsinki, Finland.
    Hiltunen, Seppo
    University of Helsinki, Finland.
    Mattsson, Markus
    University of Helsinki, Finland.
    Kallio, Sakari
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Finland.
    The impact of hypnotic suggestions on reaction times in continuous performance test in adults with ADHD and healthy controls2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0126497Article in journal (Refereed)
    Abstract [en]

    Attention is one of the key factors in both hypnotic processes and patients with ADHD. In addition, the brain areas associated with hypnosis and ADHD overlap in many respects. However, the use of hypnosis in ADHD patients has still received only minor attention in research. The main purpose of the present work was to investigate whether hypnosis and hypnotic suggestions influence the performance of adult ADHD (n = 27) and control participants (n = 31) in the continuous performance test (CPT). The hypnotic susceptibility of the participants was measured by the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A) and the attentional task was a three minute long auditory version of the CPT. The CPT task was administered four times: before hypnosis (CPT1), after a hypnotic induction (CPT2), after suggestions about speed and accuracy (CPT3), and after the termination of hypnosis (CPT4). The susceptibility of the groups measured by HGSHS:A did not differ. There was a statistically significant decrease in reaction times in both ADHD and control groups between CPT2 and CPT3. The differences between CPT1 and CPT2, even though non-significant, were different in the two groups: in the ADHD group reaction times decreased whereas in the control group they increased. Both groups made very few errors in the short CPT. This study indicates that hypnotic suggestions have an effect on reaction times in the sustained attention task both in adult ADHD patients and control subjects. The theoretical and clinical implications are discussed.

  • 533.
    Visuttijai, Kittichate
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Medical and Clinical Genetics, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Cellular, Molecular and Functional Characterization of the Tumor Suppressor Candidate MYO1C2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tumor suppressor genes play a role as a growth regulator and a gatekeeper of a cell. Their inactivation is often detected in malignant tumors. Identification of novel tumor suppressor gene candidates may help to further understand tumorigenesis and aid in the discovery of a new treatment leading toward cure of cancer.

    This PhD research project aimed to understand functional significance of a novel tumor suppressor gene candidate, myosin IC (MYO1C) and to identify potential interaction(s) of the MYO1C protein with key components of the signaling pathways involving in cancer development.

    In an experimental rat model for endometrial carcinoma (EC), detailed molecular genetic analysis of a candidate tumor suppressor region located distal to the tumor protein 53 (Tp53) suggested the myosin IC gene (Myo1c) as the best potential target for deletion of the genetic material. The question arising was whether and how MYO1C could function as a tumor suppressor gene. By using qPCR, Western blot or immunohistochemistry analyses, we examined MYO1C protein level in panels of well-stratified human colorectal cancer (CRC) and EC respectively. We found that MYO1C was significantly down-regulated in these cancer materials and that for the EC panel, the observed down-regulation of MYO1C correlated with tumor stage, where tumors at more advanced stages had less expression of MYO1C. In cell transfection experiments, we found that over-expression of MYO1C significantly decreased cell proliferation, and silencing MYO1C with siRNA increased cell viability. Additionally, knockdown of MYO1C impaired the ability of cells to migrate, spread and adhere to the surface. Recent published studies suggested a potential interplay between MYO1C and the phosphoinositide 3-kinase (PI3K)/AKT pathway. To examine this hypothesis, we analyzed the expression and/or activation of components of the PI3K/AKT and RAS/ERK signaling pathways in vivo in CRC samples, and in vitro in cells transfected with the MYO1C gene expression construct or MYO1C-targeted siRNA. To identify other potential pathways/ mechanisms through which MYO1C may exert its tumor suppressor activity, we additionally performed new sets of MYO1C-siRNA knockdown experiments. At different time points post transfection, we performed microarray global gene expression experiments followed by bioinformatics analysis of the data. Altogether, the results suggested an early PI3K/AKT response to altered MYO1C expression. We additionally identified several cancer-related genes/pathways with late response to MYO1C knockdown. All things considered, the identification of MYO1C-expression impact on cell proliferation, migration, and adhesion in combination with its interplay between several cancer-related genes and signaling pathways provide further evidence for the initial hypothesis of a tumor suppressor activity of MYO1C. 

  • 534.
    Visuttijai, Kittichate
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Medical and Clinical Genetics, Sahlgrenska Academy, University of Gothenburg.
    Pettersson, Jennifer
    Department of Medical and Clinical Genetics, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Mehrbani Azar, Yashar
    University of Skövde, School of Bioscience.
    van den Bout, Iman
    Department of physiology, Faculty of Health Sciences, University of Pretoria, South Africa.
    Örndal, Charlotte
    Department of Pathology, Sahlgrenska University Hospital, Gothenburg.
    Marcickiewicz, Janusz
    Department of Obstetrics and Gynecology, Halland Hospital Varberg, Varberg.
    Nilsson, Staffan
    Institute of Mathematical Statistics, Chalmers University of Technology, Gothenburg.
    Hörnquist, Michael
    Department of Science and Technology, University of Linköping, Norrköping.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ejeskär, Katarina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Behboudi, Afrouz
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Lowered Expression of Tumor Suppressor Candidate MYO1CStimulates Cell Proliferation, Suppresses Cell Adhesion and Activates AKT2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164063Article in journal (Refereed)
    Abstract [en]

    Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.

  • 535.
    Vrasdonk, Emke
    et al.
    Chalmers University of Technology.
    Palme, Ulrika
    Chalmers University of Technology.
    Lennartsson, Tommy
    Swedish University of Agricultural Sciences, Uppsala.
    Antonelli, Alexandre
    University of Gothenburg.
    Berg, Sofia
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jonsson, Annie
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Cederberg, Christel
    Chalmers University of Technology.
    Defining the reference situation for biodiversity in Life Cycle Assessments: Review and recommendations2016Conference paper (Refereed)
  • 536.
    Wallander, Märit
    et al.
    Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden / Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Axelsson, Kristian
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden / Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Anna G.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Lundh, Dan
    University of Skövde, School of Bioscience.
    Lorentzon, Mattias
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly - A Study from the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO)2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 3, p. 449-460Article in journal (Refereed)
    Abstract [en]

    Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (80.8 ± 8.2 years (mean ± SD), 58% women) from the Swedish registry "Senior Alert" and linked the data to several nation-wide registers. We identified 79,159 individuals with T2DM (45% with insulin (T2DM-I), 41% with oral antidiabetics (T2DM-O), and 14% with no antidiabetic treatment (T2DM-none)), and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox-regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted Hazard Ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]) and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (HR 1.22 [1.16-1.29]) and T2DM-O (HR 1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was seen regarding other fractures (any, upper arm, ankle and major osteoporotic fracture) but not for wrist fracture. Subset-analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily seen in insulin-treated patients, while the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication. This article is protected by copyright. All rights reserved.

  • 537.
    Walleczek, Jan
    et al.
    Phenoscience Laboratories, Berlin, Germany.
    Grössing, Gerhard
    Austrian Institute for Nonlinear Studies, Akademiehof, Austria.
    Pylkkänen, Paavo
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Philosophy, History, and Art Studies, University of Helsinki, Helsinki, Finland.
    Hiley, Basil
    Department of Physics and Astronomy, University College London, London, United Kingdom.
    Emergent quantum mechanics: David Bohm Centennial perspectives2019In: Entropy, ISSN 1099-4300, E-ISSN 1099-4300, Vol. 21, no 2, article id 113Article in journal (Refereed)
    Abstract [en]

    Emergent quantum mechanics (EmQM) explores the possibility of an ontology for quantum mechanics. The resurgence of interest in realist approaches to quantum mechanics challenges the standard textbook view, which represents an operationalist approach. The possibility of an ontological, i.e., realist, quantum mechanics was first introduced with the original de Broglie-Bohm theory, which has also been developed in another context as Bohmian mechanics. This Editorial introduces a Special Issue featuring contributions which were invited as part of the David Bohm Centennial symposium of the EmQM conference series (www.emqm17.org). Questions directing the EmQM research agenda are: Is reality intrinsically random or fundamentally interconnected? Is the universe local or nonlocal? Might a radically new conception of reality include a form of quantum causality or quantum ontology? What is the role of the experimenter agent in ontological quantum mechanics? The Special Issue also includes research examining ontological propositions that are not based on the Bohm-type nonlocality. These include, for example, local, yet time-symmetric, ontologies, such as quantum models based upon retrocausality. This Editorial provides topical overviews of thirty-one contributions which are organized into seven categories to provide orientation. 

  • 538.
    Walleczek, Jan
    et al.
    Phenoscience Laboratories, Berlin, Germany.
    Grössing, GerhardAustrian Institute for Nonlinear Studies, Vienna, Austria.Pylkkänen, PaavoUniversity of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Philosophy, History, and Art Studies, University of Helsinki, Helsinki, Finland.Hiley, BasilUniversity College of London, UK.
    Emergent Quantum Mechanics: David Bohm Centennial Perspectives2019Collection (editor) (Refereed)
  • 539.
    Wallenberg, Julius
    University of Skövde, School of Bioscience.
    The Neural Correlates of Aesthetic Appreciation2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In everyday life, people all over the world come across art in some way, and the question of what constitutes an aesthetic experience has long been an interesting topic for humanistic and philosophical studies. Recently, neuroscientists have begun pinning down the neural correlates of artistic production and appreciation, sparking a whole new subfield within cognitive neuroscience, known as neuroaesthetics. Most studies have focused on the relationship between brain mechanisms and the appreciation of visual art, which has shown to be a meaningful and interesting complement to empirical aesthetics and psychology. By means of several modern measuring instruments and tools such as functional magnetic resonance imaging and magnetoencephalography, neuroscientists have successfully been able to observe specific brain activity in relation to specific aesthetic activities, such as viewing paintings or artworks. In this thesis, the supposed neural correlates of aesthetic appreciation are examined through critical investigations, where evidence from some of the more outstanding studies is reviewed and compared, as well as the different problems and complexities that the field is dealing with. Furthermore, the evolutionary history of aesthetic experiences and philosophical theories on aesthetics are also examined, as well as how certain neural deficits affect our cognitive and emotional abilities to appreciate art. The findings demonstrated in this thesis show that aesthetic appreciation is a multifaceted phenomenon, depending on specific neural interactions between bottom-up sensory processing areas, reward-related subcortical structures and top-down cortical processing areas, that all together form the experience of enjoying artworks across different sensory modalities.

  • 540.
    Wallenhammar, Ann-Charlotte
    et al.
    HS Konsult AB, Örebro, Sweden.
    Algerin, Maria
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ny metod bedömer risk för bomullsmögel2017In: Arvensis, ISSN 2000-0871, no 3Article in journal (Other academic)
  • 541.
    Wallner, Fredrik K.
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Redoxis AB/ProNoxis AB, Lund, Sweden / Wallner Medicinal Chemistry AB, Göteborg, Sweden.
    Hultquist Hopkins, Malin
    Redoxis AB/ProNoxis AB, Lund, Sweden.
    Woodworth, Nina
    Redoxis AB/ProNoxis AB, Lund, Sweden.
    Lindvall Bark, Therese
    Redoxis AB/ProNoxis AB, Lund, Sweden.
    Olofsson, Peter
    Redoxis AB/ProNoxis AB, Lund, Sweden.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Correlation and cluster analysis of immunomodulatory drugs based on cytokine profiles2018In: Pharmacological Research, ISSN 1043-6618, E-ISSN 1096-1186, Vol. 128, p. 244-251Article in journal (Refereed)
    Abstract [en]

    Drug discovery is a constant struggle to overcome hurdles posed by the complexity of biological systems. One of these hurdles is to find and understand the molecular target and the biological mechanism of action. Although the molecular target has been determined, the true biological effect may be unforeseen also for well-established drugs. Hence, there is a need for novel ways to increase the knowledge of the biological effects of drugs in the developmental process. In this study, we have determined cytokine profiles for 26 non-biological immunomodulatory drugs or drug candidates and used these profiles to cluster the compounds according to their effect in a preclinical ex vivo culture model of arthritis. This allows for prediction of functions and drug target of a novel drug candidate based on profiles obtained in this study. Results from the study showed that the JAK inhibitors tofacitinib and ruxolitinib formed a robust cluster and were found to have a distinct cytokine profile compared to the other drugs. Another robust cluster included the calcineurin inhibitors cyclosporine A and tacrolimus and the protein kinase inhibitors fostamatinib disodium and sotrastaurin acetate, which caused a strong overall inhibition of the cytokine production. The results of this methodology indicate that cytokine profiles can be used to provide a fingerprint-like identification of a drug as a tool to benchmark novel drugs and to improve descriptions of mode of action.

  • 542.
    Wallner, Fredrik K.
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Redoxis AB, Lund, Sweden.
    Hultqvist Hopkins, Malin
    Redoxis AB, Lund, Sweden.
    Lindvall, Therese
    Redoxis AB, Lund, Sweden.
    Olofsson, Peter
    Redoxis AB, Lund, Sweden.
    Tilevik, Andreas
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Cytokine correlation analysis based on drug perturbation2017In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 90, p. 73-79Article in journal (Refereed)
    Abstract [en]

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

  • 543.
    Weishaupt, Holger
    et al.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Johansson, Patrik
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Sundström, Anders
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Lubovac-Pilav, Zelmina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nelander, Sven
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Swartling, Fredrik J.
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Batch-normalization of cerebellar and medulloblastoma gene expression datasets utilizing empirically defined negative control genes2019In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 35, no 18, p. 3357-3364Article in journal (Refereed)
    Abstract [en]

    Motivation: Medulloblastoma (MB) is a brain cancer predominantly arising in children. Roughly 70% of patients are cured today, but survivors often suffer from severe sequelae. MB has been extensively studied by molecular profiling, but often in small and scattered cohorts. To improve cure rates and reduce treatment side effects, accurate integration of such data to increase analytical power will be important, if not essential.

    Results: We have integrated 23 transcription datasets, spanning 1350 MB and 291 normal brain samples. To remove batch effects, we combined the Removal of Unwanted Variation (RUV) method with a novel pipeline for determining empirical negative control genes and a panel of metrics to evaluate normalization performance. The documented approach enabled the removal of a majority of batch effects, producing a large-scale, integrative dataset of MB and cerebellar expression data. The proposed strategy will be broadly applicable for accurate integration of data and incorporation of normal reference samples for studies of various diseases. We hope that the integrated dataset will improve current research in the field of MB by allowing more large-scale gene expression analyses.

  • 544.
    Wester, Jonas
    University of Skövde, School of Bioscience.
    Hur påverkas fisksamhällen av kemiska och fysikaliska faktorer: En jämförelse av fiskfauna mellan Tidaholm och Tibro2019Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    I augusti år 2018 genomfördes två provfisken i ån Tidan på platserna Tibro och Tidaholm. Syftet med studien var att titta påom artdiversiteten skiljer sig mellan två olika och skilda lokaler i samma vattendrag. I studien diskuteras också vadlikheter och skillnaderi artsamhällenas sammansättning kanbero på. I studiengranskas artiklar,kemiska förutsättningar och bakgrundsfakta. Ibörjan av artikelnförklaras syftet och frågeställningarna som denna studien utgick ifrån. I metoden förklaras hur provfisketär genomfört och beräkningar som ligger till grund för denna studien. Tillvägagångsättetför att kunna genomföra en liknade studie eller en fortsättning av denna studieförklaras i texten. Resultaten presenterar skillnader i markanvändning och jämför artdiversiteten mellan lokalerna. I studienkan man läsa om hur markanvändningen skiljer sig mellan lokalerna och granskning av fångstdata genom olika diversitets index och chi square test. En diskussion som tas uppär markanvändningen och hur stor påverkan den har på vattendraget samt hur renhållning i vattendrag kan påverka mångfalden och göra ett vattendrag mer enahanda utan tydliga variationer och så vidare. Valet av platser som näten placerades på diskuteras samt fångsteffektiviteten avnäten och representationen av färna i Tidaholm diskuteras.Vattenmiljöer kan ha många olika utseende och fysiska och kemiska förutsättningar men vad är fiskars möjligheter att anpassa sig till dessa olika förhållanden. Fiskarter är i toppen av näringskedjan och bör visa på om något inte står rätt till i vattendraget men fiskar är också väldigt anpassningsbara och många arter trivs i en mängd olika miljöer. Många fiskarter kan man hitta i nästan alla svenska vatten och det gör det svårt att säga nått om deras favorithabitat men en avsaknad av dessa arter kan säga mycket om vattendraget,så en god mångfald är ett bra betyg för många vatten. Mängden speciella habitat är också ett gott betyg för ett vatten som strävar efter en stor mångfald, utan dessa habitat sjunker mångfalden och förutsättningarna för mer habitatkrävande arter kan möjligen försvinna.

  • 545.
    Wiberg, Anders
    University of Skövde, School of Bioscience.
    Motivation: Definitioner, neurala mekanismer och nucleus accumbens roll i motivation2019Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [sv]

    Frågan om människans drivkrafter och vad som ligger bakom våra handlingar har en lång historia och ju mer man har försökt att förklara och definiera begreppet motivation desto mer komplext tycks det ha blivit. Den här uppsatsens syfte är att ge en förståelse till komplexiteten kring problematiken om begreppet motivation. Detta görs genom att belysa dess djupa rötter i filosofins och psykologins värld samt lyfta fram några av motivationsteorierna ur den omfattande breda litteraturen som skrivits om ämnet. Vidare genom att belysa vad den moderna neurovetenskapliga forskningen har tillfört i studierna om motivation. Resultatet visar på att de gamla klassiska motivationsteorierna än idag influerar på ämnet. Självbestämmandeteorin (SDT) visar på att det finns olika typer av motivation och att vi föds med tre psykologiska behov som ligger till grund för en individs intrinsiska och extrinsiska motivation. Den affektiva neurovetenskapen visar på att det finns en ömsesidig interaktion mellan kognition, affektion och beteende som baseras på djupa evolutionära emotionella rötter djupt in i det limbiska systemet. Bevis finns för att nucleus accumbens (NAc) spelar en viktig roll i val av handlingsalternativ som underlättar och effektiviserar målorienterat beteende samt har både exciterande och inhiberande funktion på beteende.

  • 546.
    Wiklund, Liselotte
    University of Skövde, School of Bioscience.
    Premenstrual Dysphoric Disorder: A Review of Neural and Cognitive Changes in Women with PMDD2017Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Around 3-8% of all women in reproductive age suffer from premenstrual dysphoric disorder (PMDD) which disenables them to live an ordinary life during the luteal phase (premenstrual phase) of the menstrual cycle. Throughout the premenstrual phase these women experience emotional, cognitive and physiological changes. Hitherto, the etiology of this disorder is unknown. Some consider the source of this state as non-biological, claiming that PMDD is a social construction imbedded in gender roles, that suggests that women should not show aggressive behavior or depressive mood unless it is during the premenstrual stage. Contradictory, research made in cognitive neuroscience claim that the origin is biological. It is assumed that the increased symptoms in women with PMDD is a result from dysfunctional sensitivity for the progesterone metabolite allopregnanolone that has a receptor in the GABAA system, hence, producing an anxious effect from high levels of allopregnanolone instead of the expected sedative, soothing effects. Research suggest that structural and functional changes occur in brain areas such as the hippocampus, parahippocampus, amygdala, cerebellum as well as in brainderived neurotrophic factor which is important for brain plasticity, growth and survival of neurons. Cognitive behaviors such as anticipation for negative stimuli, working memory and lack of cognitive control also seem to be affected by PMDD. Nonetheless, the evidence is inconsistent, the area of research face multiple issues in regards to study designs, hence making generalization at this point difficult. In sum, this essay reviews recent studies conducted in neuroscience of cognitive changes in women with PMDD, with focus on functional, structural and behavioral changes between the phases of the cycle.

  • 547.
    Wintner, Birgit
    University of Skövde, School of Bioscience.
    "Night, night, sleep tight": Effects of exercise and light on sleep physiology2018Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
  • 548.
    Yewale, Priti Prabhakar
    et al.
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Lokhande, Kiran Bharat
    Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Sridhar, Aishwarya
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Vaishnav, Monika
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Khan, Faisal Ahmad
    The Life Science Centre-Biology, School of Science and Technology, Örebro University, Sweden.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Swamy, Kakumani Venkateswara
    Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Jass, Jana
    The Life Science Centre-Biology, School of Science and Technology, Örebro University, Sweden.
    Nawani, Neelu
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
    Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors2019In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499Article in journal (Refereed)
    Abstract [en]

    Polluted waters are an important reservoir for antibiotic resistance genes and multidrug-resistant bacteria. This report describes the microbial community, antibiotic resistance genes, and the genetic profile of extended spectrum β-lactamase strains isolated from rivers at, Pune, India. ESBL-producing bacteria isolated from diverse river water catchments running through Pune City were characterized for their antibiotic resistance. The microbial community and types of genes which confer antibiotic resistance were identified followed by the isolation of antibiotic-resistant bacteria on selective media and their genome analysis. Four representative isolates were sequenced using next generation sequencing for genomic analysis. They were identified as Pseudomonas aeruginosa, Escherichia coli, and two isolates were Enterobacter cloacae. The genes associated with the multidrug efflux pumps, such as tolC, macA, macB, adeL, and rosB, were detected in the isolates. As MacAB-TolC is an ABC type efflux pump responsible for conferring resistance in bacteria to several antibiotics, potential efflux pump inhibitors were identified by molecular docking. The homology model of their MacB protein with that from Escherichia coli K12 demonstrated structural changes in different motifs of MacB. Molecular docking of reported efflux pump inhibitors revealed the highest binding affinity of compound MC207-110 against MacB. It also details the potential efflux pump inhibitors that can serve as possible drug targets in drug development and discovery. 

  • 549.
    Yewale, Priti Prabhakar
    et al.
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Maharashtra, Pune, India.
    Rahman, Aminur
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nahar, Noor
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Saha, Anandakumar
    Department of Zoology, University of Rajshahi, Rajshahi, Bangladesh.
    Jass, Jana
    The Life Science Center, The School of Science and Technology, Örebro University, Örebro, Sweden.
    Mandal, Abul
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Nawani, Neelu N.
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India.
    Sources of Metal Pollution, Global Status, and Conventional Bioremediation Practices2017In: Handbook of Metal–Microbe Interactions and Bioremediation / [ed] Surajit Das, Hirak Ranjan Dash, Boca Raton, FL: CRC Press, 2017, p. 25-40Chapter in book (Refereed)
    Abstract [en]

    Pollution control has become a priority task for global regulatory authorities. The framing of regulations, guidelines, and implementation of pollution awareness and control programs has begun at a massive scale. Heavy metals that are one of the most challenging pollutants that affect humans, animals, plants, and the ecosystem health. The sources of different metals and their toxicities are described. Current approaches in bioremediation are addressed along with the challenges posed by them. Furthermore, recent developments in biotechnology that offer novel ways to recover metals from contaminated sites are discussed.

  • 550.
    Yngve, Sara
    University of Skövde, School of Bioscience.
    Optimization of PCR Sensitivity for Detection of Bacterial Species in Blood of Patients with Suspected Sepsis2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Sepsis is commonly caused by bacteria, fungi or both present in the blood stream during inflammation. In response, inflammatory cascades are released in multiple organ systems which if prolonged causes sepsis and can eventually lead to organ failure and death. The major diagnostic technique of sepsis is blood culturing. However, the technique is time consuming and lacks sensitivity; especially in patients under antimicrobial therapy. Molecular techniques particularly PCR could possibly become implemented in sepsis diagnostics in the future. The aim of the thesis was to compare the effect on PCR sensitivity by different PCR kits, with optimized PCR conditions to find an ideal Real-time PCR applicable for direct detection of rRNA or rDNA in whole blood, using the 16S rDNA gene. The study also surveyed the overall background flora of bacterial species circulating in the blood. During the optimization Haemophillus influenzae and Streptococcus pneumoniae were added to whole blood, rRNA or rDNA was isolated and extracted and subsequently processed by Real-time PCR. Four commercially available PCR kits were compared. Attempts using rRNA did not significantly increase the PCR sensitivity. LightCycler FastStart DNA Master SYBR Green I kit (Roche Diagnostics) used for rDNA, generated low cp-values, the cleanest sequences and the finest separation between amplification curves. Twenty whole blood and pre-cultured patient samples were processed by the optimized PCR. The effect on PCR sensitivity by pre-culturing patient blood samples was studied and no statistical difference was noted. Increased PCR sensitivity is essential for implementation of PCR techniques in sepsis diagnostics.

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