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DNA methylation classifier to diagnose pancreatic ductal adenocarcinoma metastases from different anatomical sites
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-11-10)Background - We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate ... -
Impact of B7-H3 expression on metastasis, immune exhaustion and JAK/STAT and PI3K/AKT pathways in clear cell renal cell carcinoma
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-11-01)Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors (TKIs) are improving the response rates of advanced renal cancer patients. However, many treated patients do not respond, making novel immune checkpoint-based immunotherapies potentially clinically beneficial only for specific groups of patients. We detected high expression of the immune checkpoint protein B7-H3 in clear ... -
The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-10-10)BACKGROUND: Resistance to chemotherapy, combined with heterogeneity among resistant tumors, represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and actionable targets for next-line treatment.<p> <p>METHODS: Bulk RNA sequencing and reverse ... -
Podoplanin expressing macrophages and their involvement in tertiary lymphoid structures in mouse models of Sjögren’s disease
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-09-17)Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren’s disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS. We induced Sjögren’s disease by ... -
Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-10-01)Isogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversibility of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present ´Cellular Phenotypic Profiling and ... -
ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-10-22)Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We ... -
Mouse liver sinusoidal endothelial cell responses to the glucocorticoid receptor agonist dexamethasone
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-10-08)Liver sinusoidal endothelial cells (LSECs) which make up the fenestrated wall of the hepatic sinusoids, are active scavenger cells involved in blood waste clearance and liver immune functions. Dexamethasone is a synthetic glucocorticoid commonly used in the clinic and as cell culture supplement. However, the response is dependent on tissue, cell type, and cell state. The aim of this study was ... -
Development of an inducer-free, virulence gene promoter-controlled, and fluorescent reporter-labeled CRISPR interference system in Staphylococcus aureus
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-08-20)The dCas9-based Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) interference (CRISPRi) gene regulation technique requires two components: a catalytically inactive Cas9 protein (dCas9) and a single-guide RNA that targets the gene of interest. This system is commonly activated by expressing dCas9 through an inducible gene promoter, but these inducers may affect cellular ... -
Aquaporin-4 deletion leads to reduced infarct volume and increased peri-infarct astrocyte reactivity in a mouse model of cortical stroke
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-06-24)Aquaporin-4 (AQP4) is the main water channel in brain and is enriched in perivascular astrocyte processes abutting brain microvessels. There is a rich literature on the role of AQP4 in experimental stroke. While its role in oedema formation following middle cerebral artery occlusion (MCAO) has been studied extensively, its specific impact on infarct volume remains unclear. This study investigated ... -
Occupational asthma in the salmon processing industry: a case series
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-08-13)Objectives - Exposure to bioaerosols in salmon processing workers is associated with occupational asthma. IgE-mediated allergy and other disease mechanisms may be involved in airway inflammation and obstruction. Knowledge about disease burden, mechanisms, phenotypes and occupational exposure is limited.<p> <p>Methods - Salmon processing workers referred to our occupational medicine clinic from ... -
WDR83/MORG1 inhibits RRAG GTPase-MTORC1 signaling to facilitate basal autophagy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-03-07)Macroautophagy/autophagy is a conserved lysosomal degradation process composed of both selective and nonselective degradation pathways. The latter occurs upon nutrient depletion. Selective autophagy exerts quality control of damaged organelles and macromolecules and is going on also under nutrient-replete conditions. Proper regulation of autophagy is vital for cellular homeostasis and prevention ... -
MORG1 limits mTORC1 signaling by inhibiting Rag GTPases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-15)Autophagy, an important quality control and recycling process vital for cellular homeostasis, is tightly regulated. The mTORC1 signaling pathway regulates autophagy under conditions of nutrient availability and scarcity. However, how mTORC1 activity is fine-tuned during nutrient availability to allow basal autophagy is unclear. Here, we report that the WD-domain repeat protein MORG1 facilitates basal ... -
Comparative genomics of quinolone-resistant Escherichia coli from broilers and humans in Norway
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-07-06)Background The usage of fluoroquinolones in Norwegian livestock production is very low, including in broiler production. Historically, quinolone-resistant Escherichia coli (QREC) isolated from Norwegian production animals rarely occur. However, with the introduction of a selective screening method for QREC in the Norwegian monitoring programme for antimicrobial resistance in the veterinary sector ... -
The cGAS-STING signaling pathway is modulated by urolithin A
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-16)During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, ... -
Medication nonadherence and associated factors in patients with tuberculosis in Wau, South Sudan: a cross- sectional study using the world health organization multidimensional adherence model
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-07-15)Background - Tuberculosis medication nonadherence is a multi-dimensional public health problem with serious consequences worldwide. There is little information available for medication nonadherence in South Sudan. This study assessed the proportion, reasons, and associated factors for nonadherence among patients with TB in Wau Municipality, South Sudan.<p> <p>Methods - A health facility based ... -
Differentiation of highly pathogenic strains of human JC polyomavirus in neurological patients by next generation sequencing
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-02-12)This study presents an in-depth analysis of Russian stub compounds in spec ‘special’ and their competition with the corresponding full adjective special’nyj ‘special’ followed by a noun. Couched in Construction Morphology the corpus-based analysis addresses four understudied areas in theoretical and Russian morphology: shortening mechanisms, competition between morphological words and multiword ... -
Label-Free Quantitative Proteomics of Oral Microbial Communities
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-06-29)The oral cavity is a habitat for different microorganisms, of which bacteria are best described. Studying different bacterial taxa and their proteins is crucial to understanding their interactions with the host and other microbes. Also, for bacteria with virulence potential, identifying novel antigenic proteins is essential to finding candidates for the development of vaccines.<p> <p>Here, a ... -
Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-03-18)Aim We aimed to investigate changes in pre-diagnostic concentrations of classic and 11-oxygenated androgens in type 2 diabetes (T2DM) cases and healthy controls, associations between androgen concentrations and T2DM, and the potential for androgens to improve the prediction of T2DM when considered in combination with established risk factors.<p> <p>Methods Androgen concentrations were analysed ... -
Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-01-02)Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and ... -
TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery
(Journal article; Tidsskriftartikkel; Peer reviewed, 2024-05-29)Ubiquitination of mitochondrial proteins provides a basis for the downstream recruitment of mitophagy machinery, yet whether ubiquitination of the machinery itself contributes to mitophagy is unknown. Here, we show that K63-linked polyubiquitination of the key mitophagy regulator TBK1 is essential for its mitophagy functions. This modification is catalyzed by the ubiquitin ligase TRIM5a and is ...
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