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  • 1.
    Ulfenborg, Benjamin
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Karlsson, Alexander
    Högskolan i Skövde, Institutionen för informationsteknologi. Högskolan i Skövde, Forskningscentrum för Informationsteknologi.
    Riveiro, Maria
    Högskolan i Skövde, Institutionen för informationsteknologi. Högskolan i Skövde, Forskningscentrum för Informationsteknologi.
    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
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Cardiovascular and Metabolic Disease Global Medicines Development Unit, AstraZeneca, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    A data analysis framework for biomedical big data: Application on mesoderm differentiation of human pluripotent stem cells2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 6, e0179613Artikel i tidskrift (Refereegranskat)
    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.

  • 2.
    Ghosheh, Nidal
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Asplund, Annika
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Edsbagge, Josefina
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Andersson, Tommy B.
    Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden / Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
    Björquist, Petter
    NovaHep Aktiebolaget, Gothenburg, Sweden.
    Andersson, Christian X.
    Takara Bio Europe Aktiebolaget, Gothenburg, Sweden.
    Carén, Helena
    Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simonsson, Stina
    Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. AstraZeneca Research and Development, Global Medicines Development Cardiovascular and Metabolic Diseases Global Medicines Development Unit, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue2017Ingår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 49, nr 8, 430-446 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 3.
    Kajonius, Petri J.
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Social and Behavioral Studies, University West, Sweden / Department of Psychology, University of Gothenburg, Sweden.
    Dåderman, Anna M.
    Department of Social and Behavioral Studies, University West, Sweden.
    Conceptualizations of Personality Disorders with the Five Factor Model-count and Empathy Traits2017Ingår i: International Journal of Testing, ISSN 1530-5058, E-ISSN 1532-7574, Vol. 17, nr 2, 141-157 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous research has long advocated that emotional and behavioral disorders are related to general personality traits, such as the Five Factor Model (FFM). The addition of section III in the latest Diagnostic and Statistical Manual of Mental Disorders (DSM) recommends that extremity in personality traits together with maladaptive interpersonal functioning, such as lack of empathy, are used for identifying psychopathology and particularly personality disorders (PD). The objective of the present study was to measure dispositions for DSM categories based on normal personality continuums, and to conceptualize these with empathy traits. We used a validated FFM-count method based on the five personality factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness), and related these to 4 empathy traits (emphatic concern, perspective-taking, fantasy, and personal distress). The results showed that FFM-based PD scores overall could be conceptualized using only two of the empathy traits, low emphatic concern and high personal distress. Further, specific dispositions for personality disorders were characterized with distinct empathy traits (e.g., histrionic with high fantasy, and paranoid with low perspective-taking). These findings may have both theoretical and practical implications in capturing potential for personality disorders with ease and efficiency.

  • 4.
    Jonsson, Tomas
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Ecology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Conditions for Eltonian Pyramids in Lotka-Volterra Food Chains2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 10912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In ecological communities consumers (excluding parasites and parasitoids) are in general larger and less numerous than their resource. This results in a well-known observation known as 'Eltonian pyramids' or the ` pyramid of numbers', and metabolic arguments suggest that this pattern is independent of the number of trophic levels in a system. At the same time, Lotka-Volterra (LV) consumer-resource models are a frequently used tool to study many questions in community ecology, but their capacity to produce Eltonian pyramids has not been formally analysed. Here, I address this knowledge gap by investigating if and when LV food chain models give rise to Eltonian pyramids. I show that Eltonian pyramids are difficult to reproduce without density-dependent mortality in the consumers, unless biologically plausible relationships between mortality rate and interaction strength are taken into account.

  • 5.
    Parthemore, Joel
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Consciousness, semiosis, and the unbinding problem2017Ingår i: Language & Communication, ISSN 0271-5309, E-ISSN 1873-3395, Vol. 54, 36-46 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Any wider discussion of semiosis must address not only how semiosis came about, in terms of evolutionary pressures and requisite cognitive infrastructure, but also – as importantly, and too easily forgotten – how human beings experience and have experienced it, and how that experience reflects (at the same time shaping) its development. Much discussion has focused on resolving how inputs from external sensory modalities combine with internal brain processes to produce unified consciousness: the so-called binding problem. One might wish to distinguish between the coming together of conscious experience in terms of underlying mechanics and the seemingly unavoidable reality that human beings experience a consciousness that is, from the onset, phenomenally unified. The unbinding problem is shown to be potentially just as important to telling the story.

    Publikationen är tillgänglig i fulltext från 2019-06-01 00:01
  • 6.
    Kajonius, Petri J.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Gothenburg, Sweden / Department of Behavioral Sciences, University West, Sweden.
    Cross-cultural personality differences between East Asia and Northern Europe in IPIP-NEO2017Ingår i: International Journal of Personality Psychology, E-ISSN 2451-9243, Vol. 3, nr 1, 1-7 s.Artikel i tidskrift (Refereegranskat)
  • 7.
    Skillbäck, Tobias
    et al.
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Delsing, Louise
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Mattsson, Niklas
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden / Department of Neurology, Skåne University Hospital, Lund, Sweden.
    Janelidze, Shorena
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Nägga, Katarina
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Kilander, Lena
    Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
    Hicks, Ryan
    Discovery Sciences, IMED Biotech Unit, AstraZeneca, Mölndal, Sweden.
    Wimo, Anders
    Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden / Division for Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
    Winblad, Bengt
    Division for Neurogeriatrics, Department of Neurobiology, Care Sciences, and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden / Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden.
    Hansson, Oskar
    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden / Department of Neurology, Skåne University Hospital, Lund, Sweden.
    Blennow, Kaj
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Eriksdotter, Maria
    Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden / Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (NVS), Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
    Zetterberg, Henrik
    Department of Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden / Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden / Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom / UK Dementia Research Institute at UCL, London, United Kingdom.
    CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 59, 1-9 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology.

  • 8.
    Wallner, Fredrik K.
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. 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
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Cytokine correlation analysis based on drug perturbation2017Ingår i: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 90, 73-79 s.Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Wobst, Heike J.
    et al.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Wesolowski, Steven S.
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Chadchankar, Jayashree
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Delsing, Louise
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. IMED Biotech Unit, AstraZeneca Discovery Science, Mölndal, Sweden.
    Jacobsen, Steven
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Mukherjee, Jayanta
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Deeb, Tarek Z.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States.
    Dunlop, John
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Brandon, Nicholas J.
    IMED Biotech Unit, AstraZeneca Neuroscience IMED, AstraZeneca, Cambridge, United States.
    Moss, Stephen J.
    AstraZeneca-Tufts Laboratory for Basic and Translational Neuroscience, Tufts University School of Medicine, Boston, United States / Department of Neuroscience, Tufts University School of Medicine, Boston, United States.
    Cytoplasmic Relocalization of TAR DNA-Binding Protein 43 Is Not Sufficient to Reproduce Cellular Pathologies Associated with ALS In vitro2017Ingår i: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, 46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in the gene TARDBP, which encodes TAR DNA-binding protein 43 (TDP-43), are a rare cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While the majority of mutations are found in the C-terminal glycine-rich domain, an alanine to valine amino acid change at position 90 (A90V) in the bipartite nuclear localization signal (NLS) of TDP-43 has been described. This sequence variant has previously been shown to cause cytoplasmic mislocalization of TDP-43 and decrease protein solubility, leading to the formation of insoluble aggregates. Since the A90V mutation has been described both in patients as well as healthy controls, its pathogenic potential in ALS and FTD remains unclear. Here we compare properties of overexpressed A90V to the highly pathogenic M337V mutation. Though both mutations drive mislocalization of the protein to the cytoplasm to the same extent, M337V produces more significant damage in terms of protein solubility, levels of pathogenic phosphorylation, and formation of C-terminal truncated protein species. Furthermore, the M337V, but not the A90V mutant, leads to a downregulation of histone deacetylase 6 and Ras GTPase-activating protein-binding protein. We conclude that in the absence of another genetic or environmental 'hit' the A90V variant is not sufficient to cause the deleterious phenotypes associated with ALS and FTD, despite prominent cytoplasmic protein relocalization of TDP-43.

  • 10.
    Bays, Harold E.
    et al.
    Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY, USA.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Global Medicines Development, CVMD, AstraZeneca, Gothenburg, Sweden.
    Xu, John
    Biometrics and Information Sciences, AstraZeneca, Gaithersburg, MD, USA.
    Sjöstrom, Carl David
    Global Medicines Development, CVMD, AstraZeneca, Gothenburg, Sweden.
    Underberg, James A.
    Department of Medicine, NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease, New York, NY, USA.
    Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels2017Ingår i: Journal of Clinical Lipidology, ISSN 1933-2874, E-ISSN 1876-4789, Vol. 11, nr 2, 450-458 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption.

    OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels.

    METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (>= 150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria.

    RESULTS: The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups.

    CONCLUSION: Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors. 

  • 11.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden / CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden.
    Andersson, Rune
    CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden / Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Usener, Barbara
    Department of Clinical Chemistry, Unilabs AB, Skövde, Sweden.
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, e018704Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.

    METHODS:

    Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).

    RESULTS:

    For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).

    CONCLUSIONS:

    Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

  • 12.
    Koivisto, Mika
    et al.
    University of Turku, Turku, Finland.
    Grassini, Simone
    University of Turku, Turku, Finland.
    Salminen-Vaparanta, Niina
    University of Turku, Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. University of Turku, Turku, Finland.
    Different Electrophysiological Correlates of Visual Awareness for Detection and Identification2017Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, nr 9, 1621-1631 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Detecting the presence of an object is a different process than identifying the object as a particular object. This difference has not been taken into account in designing experiments on the neural correlates of consciousness. We compared the electrophysiological correlates of conscious detection and identification directly by measuring ERPs while participants performed either a task only requiring the conscious detection of the stimulus or a higher-level task requiring its conscious identification. Behavioral results showed that, even if the stimulus was consciously detected, it was not necessarily identified. A posterior electrophysiological signature 200-300 msec after stimulus onset was sensitive for conscious detection but not for conscious identification, which correlated with a later widespread activity. Thus, we found behavioral and neural evidence for elementary visual experiences, which are not yet enriched with higher-level knowledge. The search for the mechanisms of consciousness should focus on the early elementary phenomenal experiences to avoid the confounding effects of higher-level processes.

  • 13.
    Olsson, Björn E.
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Korsakova, Ekaterina S.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Anan'ina, Lyudmila N.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Pyankova, Anna A.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Olga V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Plotnikova, Elena G.
    Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, Perm, Russia.
    Mavrodi, Dmitri V.
    Department of Biological Sciences, The University of Southern Mississippi, USA.
    Draft genome sequences of strains Salinicola socius SMB35T, Salinicola sp. MH3R3–1 and Chromohalobacter sp. SMB17 from the Verkhnekamsk potash mining region of Russia2017Ingår i: Standards in Genomic Sciences, ISSN 1944-3277, E-ISSN 1944-3277, Vol. 12, nr 39, 1-13 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Halomonads are moderately halophilic bacteria that are studied as models of prokaryotic osmoadaptation and sources of enzymes and chemicals for biotechnological applications. Despite the progress in understanding the diversity of these organisms, our ability to explain ecological, metabolic, and biochemical traits of halomonads at the genomic sequence level remains limited. This study addresses this gap by presenting draft genomes of Salinicola socius SMB35T, Salinicola sp. MH3R3-1 and Chromohalobacter sp. SMB17, which were isolated from potash mine tailings in the Verkhnekamsk salt deposit area of Russia. The analysis of these genomes confirmed the importance of ectoines and quaternary amines to the capacity of halomonads to tolerate osmotic stress and adapt to hypersaline environments. The study also revealed that Chromohalobacter and Salinicola share 75-90% of the predicted proteome, but also harbor a set of genus-specific genes, which in Salinicola amounted to approximately 0.5 Mbp. These genus-specific genome segments may contribute to the phenotypic diversity of the Halomonadaceae and the ability of these organisms to adapt to changing environmental conditions and colonize new ecological niches.

  • 14.
    Sikka, Pilleriin
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Sandman, Nils
    Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland / The Genomics and Biomarkers Unit, National Institute for Health and Welfare, Finland.
    Tuominen, Jarno
    Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Dream emotions: a comparison of home dream reports with laboratory early and late REM dream reports2017Ingår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, 1-9 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to compare the emotional content of dream reports collected at home upon morning awakenings with those collectedin the laboratory upon early and late rapid eye movement (REM) sleep awakenings. Eighteen adults (11 women, seven men; mean age = 25.89 ± 4.85) wrote down their home dreams every morning immediately upon awakening during a 7-day period. Participants also spent two non-consecutive nights in the sleep laboratory where they were awoken 5 min into each continuous REM sleep stage, upon which they gave a verbal dream report. The content of a total of 151 home and 120 laboratory dream reports was analysed by two blind judges using the modified Differential Emotions Scale. It was found that: (1) home dream reports were more emotional than laboratory early REM dream reports, but not more emotional than laboratory late REM dream reports; (2) home dream reports contained a higher density of emotions than laboratory (early or late REM) dream reports; and (3) home dream reports were more negative than laboratory dream reports, but differences between home and early REM reports were larger than those between home and late REM reports. The results suggest that differences between home and laboratory dream reports in overall emotionality may be due to the time of night effect. Whether differences in the density of emotions and negative emotionality are due to sleep environment or due to different reporting procedures and time spent in a sleep stage, respectively, remains to be determined in future studies.

  • 15.
    Hurme, Mikko
    et al.
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Koivisto, Mika
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Railo, Henry
    Department of Psychology, University of Turku, Finland / Centre for Cognitive Neuroscience, University of Turku, Finland / Turku Brain and Mind Centre, University of Turku, Finland.
    Early processing in primary visual cortex is necessary for conscious and unconscious vision while late processing is necessary only for conscious vision in neurologically healthy humans2017Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 150, 230-238 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The neural mechanisms underlying conscious and unconscious visual processes remain controversial. Blindsight patients may process visual stimuli unconsciously despite their VI lesion, promoting anatomical models, which suggest that pathways bypassing the VI support unconscious vision. On the other hand, physiological models argue that the major geniculostriate pathway via VI is involved in both unconscious and conscious vision, but in different time windows and in different types of neural activity. According to physiological models, feedforward activity via VI to higher areas mediates unconscious processes whereas feedback loops of recurrent activity from higher areas back to VI support conscious vision. With transcranial magnetic stimulation (TMS) it is possible to study the causal role of a brain region during specific time points in neurologically healthy participants. In the present study, we measured unconscious processing with redundant target effect, a phenomenon where participants respond faster to two stimuli than one even when one of the stimuli is not consciously perceived. We tested the physiological feedforward-feedback model of vision by suppressing conscious vision by interfering selectively either with early or later VI activity with TMS. Our results show that early VI activity (60 ms) is necessary for both unconscious and conscious vision. During later processing stages (90 ms), VI contributes selectively to conscious vision. These findings support the feedforward-feedback-model of consciousness.

  • 16.
    Retz, Karolina
    et al.
    Department of Clinical Microbiology, Unilabs AB, Skövde.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Andersson, Carl
    Högskolan i Skövde.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Ljungström, Lars
    The Skaraborg Hospital, Skövde, Sweden .
    Enroth, Helena
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde .
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting2017Konferensbidrag (Refereegranskat)
  • 17.
    Toräng, Per
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi. Högskolan i Skövde, Institutionen för biovetenskap. 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 plant2017Ingår i: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, nr 9, 2206-2218 s.Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Nahar, Nour
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Rahman, Aminur
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Ghosh, Sibdas
    School of Arts and Science, Iona College, New Rochelle, NY, USA.
    Nawani, Neelu
    Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, India.
    Mandal, Abul
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Functional studies of AtACR2 gene putatively involved in accumulation, reduction and/or sequestration of arsenic species in plants2017Ingår i: Biologia (Bratislava), ISSN 0006-3088, E-ISSN 1336-9563, Vol. 72, nr 5, 520-526 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Food-based exposure to arsenic is a human carcinogen and can severely impact human health resulting in many cancerous diseases and various neurological and vascular disorders. This project is a part of our attempts to develop new varieties of crops for avoiding arsenic contaminated foods. For this purpose, we have previously identified four key genes, and molecular functions of two of these, AtACR2 and AtPCSl, have been studied based on both in silico and in vivo experiments. In the present study, a T-DNA tagged mutant, (SALK-143282C with mutation in AtACR2 gene) of Arabidopsis thaliana was studied for further verification of the function of AtACR2 gene. Semi-quantitative RT-PCR analyses revealed that this mutant exhibits a significantly reduced expression of the AtACR2 gene. When exposed to 100 μM of arsenate (AsV) for three weeks, the mutant plants accumulated arsenic approximately three times higher (778 μg/g d. wt.) than that observed in the control plants (235 μg/g d. wt.). In contrast, when the plants were exposed to 100 μM of arsenite (AsIII), no significant difference in arsenic accumulation was observed between the control and the mutant plants (535 μg/g d. wt. and 498 μg/g d. wt., respectively). Also, when arsenate and arsenite was measured separately either in shoots or roots, significant differences in accumulation of these substances were observed between the mutant and the control plants. These results suggest that AtACR2 gene is involved not only in accumulation of arsenic in plants, but also in conversion of arsenate to arsenite inside the plant cells. © 2017 Institute of Molecular Biology, Slovak Academy of Sciences.

    Publikationen är tillgänglig i fulltext från 2018-06-01 00:01
  • 19.
    Rahman, Aminur
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. The Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    Olsson, Björn
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Jass, Jana
    The Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    Nawani, Neelu
    Microbial Diversity Research Centre, Dr. D.Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune-411033, India.
    Ghosh, Sibdas
    School of Arts and Science, Iona College, New Rochelle, NY 10801, USA.
    Mandal, Abul
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Genome Sequencing Revealed Chromium and Other Heavy Metal Resistance Genes in E. cloacae B2-Dha2017Ingår i: Journal of Microbial & Biochemical Technology, ISSN 1948-5948, E-ISSN 1948-5948, Vol. 9, nr 5, 191-199 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The previously described chromium resistant bacterium, Enterobacter cloacae B2-DHA, was isolated from leather manufacturing tannery landfill in Bangladesh. Here we report the entire genome sequence of this bacterium containing chromium and other heavy metal resistance genes. The genome size and the number of genes, determined by massive parallel sequencing and comparative analysis with other known Enterobacter genomes, are predicted to be 4.22 Mb and 3958, respectively. Nearly 160 of these genes were found to be involved in binding, transport, and catabolism of ions as well as efflux of inorganic and organic compounds. Specifically, the presence of two chromium resistance genes, chrR and chrA was verified by polymerase chain reaction. The outcome of this research highlights the significance of this bacterium in bioremediation of chromium and other toxic metals from the contaminated sources.

  • 20.
    Sikka, Pilleriin
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Feilhauer, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Valli, Katja
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    Revonsuo, Antti
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Centre for Cognitive Neuroscience, Department of Psychology, University of Turku, Finland.
    How You Measure Is What You Get: Differences in Self- and External Ratings of Emotional Experiences in Home Dreams2017Ingår i: American Journal of Psychology, ISSN 0002-9556, E-ISSN 1939-8298, Vol. 130, nr 3, 367-384 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study demonstrates that different methods for measuring emotional experiences in dreams — self-ratings of dreams using emotion rating scales versus external ratings in the form of content analysis of narrative dream reports — can lead to strikingly different results and contradicting conclusions about the emotional content of home dreams. During 3 consecutive weeks, every morning upon awakening, 44 participants (16 men, 28 women, average age 26.9± 5.1 years) reported their dreams and rated their emotional experiences in those dreams using the modified Differential Emotions Scale. Two external judges rated emotional experiences inthe same 552 (M = 12.55 ± 5.72) home dream reports using the same scale. Comparison of the 2 methods showed that with self-ratings dreams were rated as more emotional and more positive than with external ratings. Moreover, whereas with self-ratings the majority of dreams was rated as positively valenced, with external ratings the majority of dream reports was rated as negatively valenced. Although self- and external ratings converge, at least partially, in the measurement of negative emotional experiences, they diverge greatly in the measurement of positive emotional experiences. On one hand, this discrepancy may result from different biases inherent in the 2 measurement methods highlighting the need to develop better methods for measuring emotional experiences. On the other hand, self- and external ratings may capture different phenomena and should thus be considered complementary and used concurrently. Nevertheless, results suggest that negative emotional experiences can be measured in a more valid and reliable manner than positive emotional experiences.

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