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  • 501.
    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. 

  • 502.
    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.

  • 503.
    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. 

  • 504.
    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.

  • 505.
    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. 

  • 506.
    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.

  • 507.
    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)
  • 508.
    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.

  • 509.
    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. 

  • 510.
    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)
  • 511.
    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.

  • 512.
    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)
  • 513.
    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.

  • 514.
    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.

  • 515.
    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.

  • 516.
    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.

  • 517.
    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
  • 518.
    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. 

  • 519.
    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.

  • 520.
    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.

  • 521.
    Álvarez-Carretero, Sandra
    University of Skövde, School of Bioscience.
    BACTpipe: Characterization of bacterial isolates based on whole-genome sequence data2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The technological advances have led to faster and more cost-effective sequencing platforms, making it quicker and more affordable to generate genomic sequence data. For the study of bacterial genome, two main methods can be used, whole-genome sequencing and metagenomic shotgun sequencing, of which the first is the mostly used in the past years.

    As a consequence of these advances, a vast amount of data is currently available and the need of bioinformatics tools to efficiently analyse and interpret it has dramatically increased. At present, there is a great quantity of tools to use in each step of bacterial genome characterization: (1) pre-processing, (2) de novo assembly, (3) annotation, and (4) taxonomic and functional comparisons. Therefore, it is difficult to decide which tools are better to use and the analysis is slowed down when changing from one tool to another. In order to tackle this, the pipeline BACTpipe was developed. This pipeline concatenates both bioinformatics tools selected based on a previous testing and additional scripts to perform the whole bacterial analysis at once. The most relevant output generated by BACTpipe are the annotated de novo assembled genomes, the newick file containing the phylogenetic relationships between species, and the gene presence-absence matrix, which the users can then filter according to their interests.

    After testing BACTpipe with a set of bacterial whole-genome sequence data, 60 genes out of the 18195 found in all the Lactobacillus species analysed were classified as core genes, i.e. genes shared among all these species. Housekeeping genes or genes involved in the replication, transcription, or translation processes were identified

  • 522.
    Ährlund-Richter, Andreas
    University of Skövde, School of Bioscience.
    Analysis of somatic mutations in papillomavirus positive tumours from younger and older oropharyngeal cancer patients2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    ABSTRACT Background: Human Papilloma Virus positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OSCC), dominated by tonsillar cancer (TSCC) and base of tongue cancer (BOTSCC) has low mutation-frequency and better survival for younger than older patients.Aim: To examine if HPV+ TSCC and BOTSCC have distinct gene-mutation profiles, for 50 often-mutated genes in cancer, in younger compared to older patients and to test and compare different variant callers to get a deeper understanding of the data.Materials and methods: DNA had previously been extracted from 299 formalin-fixed-paraffin-embedded (FFPE) tumor biopsies and 13 normal samples, and sequenced on the Ion Proton sequencer, a NGS (Next-Generation Sequencing) platform. Alignment and variant calling had been performed via the Ion Torrent Suite software v5 (ITS), and Torrent Variant Caller (TVC).UPPMAX, a High-Performance-Computational cluster (HPC) at Uppsala University was used for storing and computing of the sequenced data. Parallel-processing was used to optimize repetitive steps, saving days of computation time. The descriptive analysis, graphical data representations, and more in-depth analysis, were done in R.Initially, variant calling was performed for 13 tumor/normal paired samples using the novel MuTect2 software from the Genome Analysis Toolkit (GATK) toolset. Variant annotation and statistical analysis was performed on all the 13 paired sequenced samples, using SnpEff. Due to a poor overlap between the above MuTect2 and TVC, after adequate filtering TVC, MuTect, Strelka and VarScan2 were also utilized for comparison.Result and Conclusion: Having only 13 normal samples, normal-tumor paired variant calling to distinguish germ line and somatic variants could not be performed. To obtain an approximation of the amount of germline variation in our cohort, additional variant callers were used for the tumor normal pairs. The data obtained with the TVC caller formed the basis for further analysis of the tumor samples.Notably, comparisons of TVC with MuTect2 output revealed major discrepancies and limited overlap. However, when comparing MuTect2 with MuTect, Strelka, or VarScan 2 regarding overlaps with TVC – the overlap were still limited, but higher degrees of overlaps were disclosed between Strelka, MuTect and MuTec2, indicating that MuTect2 was a successful further development and successor of MuTect.Evidence for presence of distinct gene-mutation profiles correlating to age could not be obtained in the analyzed tumor cohort with the software tool kits applied. Statistical analysis using Wilcoxon-Mann Whitney test did not support a hypothesis of distinct age related mutations for any of the 50 genes analyzed in this tumor cohorts.The highest p-value for the Wilcoxon-Mann Whitney test was for the gene APC, at p ~ 0.054 hints at a possible connection. However, more extensive research with more samples sequenced is necessary to confirm or reject this correlation.

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