Evaluating the effects of long term exposure to environmental relevant concentrations of real life mixtures of persistent organic pollutants (POPs) in the zebrafish model.

Persistent organic pollutants (POPs) have been widely distributed throughout the world for decades and while the use of some have been phased out, others are still being utilised and their levels are rising in biota. Levels detected in tissue and blood samples have caused for a growing concern for their potential effects on humans and wildlife and many effects studies have been performed. Focus for research has, however, mainly been on high concentrations of single compounds, although it is the realistic levels of real life mixtures of compounds found in the environment that may possess such a threat. In this study, we have investigated the long term effects of environmentally relevant levels of real life mixtures of POPs using the zebrafish as a biomonitor organism. Burbots (Lota lota) from two sites within the same freshwater system in Norway, Lake Mjøsa and Lake Losna, with different history of pollution, were captured and POPs extracted from the liver oil. Zebrafish were exposed indirectly, by exposing their live-food, from start of feeding and until sexual maturation to either the Losna mixture or to one of three dose levels of the Mjøsa mixture. Survival was monitored throughout the experiment while other demographic variables such as growth and sex ratio were evaluated at the time of sexual maturity. Traditional (protein) biomarkers for EROD activity and vitellogenin induction were also measured in addition to organ-specific differences in gene expression pattern using microarray analysis. Exposure resulted in significant lower survival rate and increased growth of the fish, while a small but significant induction was observed in the EROD activity. Analysis of gene expression patterns revealed small changes in mRNA levels though differences were clearly seen. The microarray assay indicated oestrogenic effects of both of the mixtures, in addition to other endocrine disrupting effects related to the steroid- and thyroid hormones. We conclude that long term exposure to real life mixtures of POPs caused direct morphological and phenotypic changes and effects systems related to development and reproduction even at low levels found in the environment, and thus may pose a potential health risk for humans and wildlife living in exposed areas or in other ways being frequently exposed to such mixtures of toxins

Naturalizing meaning : Jerry Fodor's Theory of content

Jerry Fodor’s Theory of Content Fodor’s project is that of providing a naturalistic account of meaning. The way in which he proposes to do this is by providing a sufficient condition for the content of mental states. This condition must, to be naturalistic, be framed in non-intentional/non-semantic terms. The account aims to provide an account of meaning that is compatible with physicalism, and is therefore very interesting from a metaphysical standpoint. The key problem Fodor’s theory wants to solve is what is called the disjunction problem. This is the problem of naturalistically specifying contents that are sufficiently fine-grained to reconstruct the contents of propositional attitudes. This is a problem common to naturalistic theories of content. Fodor seeks to solve this problem by appealing to asymmetric dependencies among causal laws. I argue that though Fodor’s proposal is the best available for naturalizing meaning it does not succeed in solving the disjunction problem and providing a naturalistic account of meaning

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Masteroppgave i arbeids- og organisasjonspsykologiMAPSYK345MAPS-PSYKMAPS-AO

FSAP Protects against Histone-Mediated Increase in Endothelial Permeability In Vitro

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iPSC-derived liver organoids and inherited bleeding disorders : potential and future perspectives

Funding: This work was made possible with funding from the Norwegian Research Council (325869) and the South-Eastern Norway Regional Health Authority (2019071).The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease.Peer reviewe

USING OF METAL DELETION TECHNIQUE FOR ARTIFACTS REDUCTION ON PLANNING COMPUTED TOMOGRAPHY SCANS

Cardiac electronic devices implanted in cancer patients can cause metal artifacts on planning computed tomography scans. The artifacts contribute inaccuracies to dose calculation received by cardiac devices and electrodes. To solve this problem we have tested Metal Deletion Technique (MDT) in Masaryk Memorial Cancer Institute. The data obtained from this experiment confirm the necessity of MDT application in medical practice

LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro

Published version. Source at http://dx.doi.org/10.1007/s00125-016-4036-y Aims/hypothesis: Activation of inflammatory pathways is involved in the pathogenesis of type 2 diabetes mellitus. On the basis of its role in vascular inflammation and in metabolic disorders, we hypothesised that the TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) could be involved in the pathogenesis of type 2 diabetes mellitus. Methods: Plasma levels of LIGHT were measured in two cohorts of type 2 diabetes mellitus patients (191 Italian and 40 Norwegian). Human pancreatic islet cells and arterial endothelial cells were used to explore regulation and relevant effects of LIGHT in vitro. Results: Our major findings were: (1) in both diabetic cohorts, plasma levels of LIGHT were significantly raised compared with sex- and age-matched healthy controls (n = 32); (2) enhanced release from activated platelets seems to be an important contributor to the raised LIGHT levels in type 2 diabetes mellitus; (3) in human pancreatic islet cells, inflammatory cytokines increased the release of LIGHT and upregulated mRNA and protein levels of the LIGHT receptors lymphotoxin β receptor (LTβR) and TNF receptor superfamily member 14 (HVEM/TNFRSF14); (4) in these cells, LIGHT attenuated the insulin release in response to high glucose at least partly via pro-apoptotic effects; and (5) in human arterial endothelial cells, glucose boosted inflammatory response to LIGHT, accompanied by an upregulation of mRNA levels of HVEM (also known as TNFRSF14) and LTβR (also known as LTBR). Conclusions/interpretation: Our findings show that patients with type 2 diabetes mellitus are characterised by increased plasma LIGHT levels. Our in vitro findings suggest that LIGHT may contribute to the progression of type 2 diabetes mellitus by attenuating insulin secretion in pancreatic islet cells and by contributing to vascular inflammation