Institutt for medisinsk biologi: Recent submissions
Now showing items 421-440 of 1154
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The effects of metformin on age-related changes in the liver sinusoidal endothelial cell
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-14)Age-related changes in the liver sinusoidal endothelium, particularly the reduction in fenestrations, contribute to insulin resistance in old age. Metformin impacts on the aging process and improves insulin resistance. Therefore, the effects of metformin on the liver sinusoidal endothelium were studied. Metformin increased fenestrations in liver sinusoidal endothelial cells isolated from both young ... -
Use of Peptide Arrays for Identification and Characterization of LIR Motifs
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-05)The mammalian ATG8 proteins (LC3A-C/GABARAP, GABARAPL1, and GABARAPL2) are small ubiquitin-like proteins critically involved in macroautophagy. Their processed C-termini are posttranslationally conjugated to a phosphatidylethanolamine moiety, enabling their insertion into the lipid bilayers of both the inner and outer membranes of the forming autophagosomes. The ATG8s bind a diverse selection of ... -
Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-28)Syntaxin 17 (Stx17) has been implicated in autophagosome-lysosome fusion. Here, we report that Stx17 functions in assembly of protein complexes during autophagy initiation. Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13<sup>+</sup>FIP200<sup>+</sup> mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 ... -
Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-15)Based on the cabozantinib scaffold, novel c‐Met inhibitors were rationalized from the limited knowledge of structure‐activity relationships for the quinoline 6‐position. Emphasis was given to modifications capable of engaging in additional polar interactions with the c‐Met active site. In addition, <i>ortho</i>‐fluorinations of the terminal benzene ring were explored. Fifteen new molecules were ... -
Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-15)<i>Background</i> - Antibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections.<p><p> <i>Aim</i> - Our objective was to compare the country-specific species distribution of the four Gram-negative species <i>Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa</i> and <i>Acinetobacter</i> species and the proportions of selected acquired ... -
Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis
(Journal article; Tidsskriftartikkel; Peer reviewed, 2018-11-05)<i>Background</i> - Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of ... -
The successful uptake and sustainability of rapid infectious disease and antimicrobial resistance point-of-care testing requires a complex 'mix-and-match' implementation package
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-02)The emergence and spread of antimicrobial resistance is one of the major global issues currently threatening the health and wealth of nations, with effective guidelines and intervention strategies urgently required. Such guidelines and interventions should ideally be targeted at individuals, communities, and nations, requiring international coordination for maximum effect. In this respect, the ... -
Homology modeling to screen for potential binding of contaminants to thyroid hormone receptor and transthyretin in glaucous gull (Larus hyperboreus) and herring gull (Larus argentatus)
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-11)Thyroid hormone disrupting chemicals (THDCs) are of major concern in ecotoxicology. With the increased number of emerging chemicals on the market there is a need to screen for potential THDCs in a cost-efficient way, and <i>in silico</i> modeling is an alternative to address this issue. In this study homology modeling and docking was used to screen a list of 626 compounds for potential thyroid hormone ... -
Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-09-11)The prometastatic stroma generated through tumor cells/host cells interaction is critical for metastatic growth. To elucidate the role of ICAM-1 on the crosstalk between tumor and primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), implicated in tumor adhesion and angiogenesis, we performed <i>in vitro</i> cocultures and an <i>in vivo</i> model of liver metastasis ... -
Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-27)Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. ... -
SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-05)The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective ... -
Simultaneous Detection of Zinc and Its Pathway Metabolites Using MALDI MS Imaging of Prostate Tissue
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-16)Levels of zinc, along with its mechanistically related metabolites citrate and aspartate, are widely reported as reduced in prostate cancer compared to healthy tissue and are therefore pointed out as potential cancer biomarkers. Previously, it has only been possible to analyze zinc and metabolites by separate detection methods. Through matrix-assisted laser desorption/ionization mass spectrometry ... -
The proposed Drug Resistance Index (DRI) is not a good measure of antibiotic effectiveness in relation to drug resistance
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-21)Summary box<p> <ul> <li>The Drug Resistance Index (DRI) is proposed as measure of antibiotic effectiveness in a given country, by combining, in a single metric the use of various antibiotic groups and the resistance proportions of several pathogens.</li> <li>The DRI is a complicated measure that gives results that cannot be understood by common knowledge and logic.</li> <li>The DRI conveys ... -
Grading of oral squamous cell carcinomas – Intra and interrater agreeability: Simpler is better?
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-03)<i>Background</i> - Numerous studies have been presented on histological grading of oral squamous cell carcinomas (OSCC) for predicting survival, but uncertainty of their usefulness rises due to discordances of results. A scoring system should be robust and well validated, and intra‐ and interrater agreement can be used as a tool to visualize the strength of reproducibility.<p><p> <i>Methods</i> ... -
Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-25)Most patients whose large bowel cancer has spread to other organs do not respond to immune therapy. We detected a rare gene mutation, termed 9p24.1 copy-number gain (CNG), in an otherwise incurable colorectal cancer that provoked an immune therapy response. We identified this gene mutation by gene-panel sequencing of DNA from a liver metastasis biopsy from a patient who had disease refractory to ... -
Human concentrations of uric acid scavenges adaptive and maladaptive ROS in isolated rat hearts subjected to ischemic stress
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-09-14)Uric acid is a purine degradation product but also an important antioxidant and ROS scavenger. Experimental settings that mimic myocardial ischemia-reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on ... -
Method for Determining Gelatinolytic Activity in Tissue: In Situ Gelatin Zymography
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019)To explore the physiological or pathological roles of proteases, it is important to be able to detect and precisely localize them in a tissue, to differentiate between inactive and active forms, as well as to quantify and determine the nature of the enzyme that degrades a given substrate. Here we present an in situ gelatin zymography method that allows for a precise localization of active gelatin-degrading ... -
Method for Determining Gelatinolytic Activity in Tissue Extracts: Real-Time Gelatin Zymography
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019)To explore the physiological or pathological roles of proteases, it is important to be able to detect and precisely localize them in a tissue, to differentiate between inactive and active forms, as well as to quantify and determine the nature of the enzyme that degrades a given substrate. Here we present a protocol for real-time gelatin zymography that is very useful for the detection of gelatin-degrading ... -
Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-09-09)Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are ... -
Exposures and Health Effects of Bioaerosols in Seafood Processing Workers - a Position Statement
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-27)Occupational hazards exist in the processing of seafood both in land-based facilities as well as on board vessels. Recent findings on occupational injury and respiratory health risks among seafood processing workers were presented and discussed at the IFISH5 conference. Particular emphasis was put on the challenges that im/migrant workers encounter, the greater risks onboard factory vessels, especially ...