Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) with neuroprotective and cardioprotective properties. It is thought that some of the actions of EPA may be attributed to its elongated metabolite, the PUFA docosapentaenoic acid (DPA). Docosahexaenoic acid (DHA) and arachidonic acid (AA) are bioactive PUFA ubiquitously expressed in neural tissues. EPA and AA can be converted by cyclooxygenase (COX) to prostanoids and by lipoxygenase (LOX) to hydroxy fatty acids. PUFA can also be converted to ethanolamides in the brain. These mediators are involved in physiological and pathological processes in many bodily systems. The purpose of this study was to examine the production of eicosanoids, hydroxy fatty acids and fatty acid ethanolamides in young and aged rat brain following EPA or DPA enriched diets. The effects of specific PUFA on human platelet eicosanoid production were also investigated as these mediators play a role in adhesion and aggregation. Liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) assays were developed and used to measure lipid mediators in rat brain and human platelets. Ageing in rat brain was accompanied with several changes in the prostanoid and hydroxy fatty acid profiles. Supplementing the diet with EPA or DPA at a daily dose of 200 mg/kg for 8 weeks prevented these changes and decreased levels of PGE2. DPA changed the profile of hydroxy fatty acids synthesised in the brain tissue of young animals. This study has shown that levels of eicosapentaenoylethanolamide (EPA-EA) increase in the brain as a result of ageing and that this is accompanied by an increase in levels of anandamide. Feeding aged animals EPA or DPA further increased the levels of EPA-EA but prevented any change in the level of anandamide. Niacin is used to treat hypercholesterolaemia although it is associated with an unpleasant PGD2 mediated skin flush. This exploratory study has shown that human platelets treated with niacin did not show any changes in their prostanoid and hydroxy fatty acid profiles. Platelets treated with EPA showed increased production of TXB3 and 12-HEPE. Niacin augmented the effects of EPA on human platelet mediator synthesis. Overall, this study has demonstrated that EPA can change brain and platelet lipid mediator synthesis and has provided evidence that could explain some of the neuroprotective and cardioprotective actions of this PUFA.

La consommation de poisson et de mammifères marins représente une source importante d’acides gras oméga-3 connus pour leurs effets bénéfiques sur le développement des fonctions cérébrales et notamment, sur le développement du système visuel. Afin de tester l’hypothèse selon laquelle l’exposition prénatale aux acides gras oméga-3 a des effets bénéfiques à long terme, nous avons examiné les fonctions visuelles chez des enfants Inuits d’âge scolaire exposés à de grandes quantités d’oméga-3 durant la période de gestation. Des enfants Inuits (n = 136; moyenne d’âge = 11.3 ans) du nord du Québec (Nunavik) ont participé à cette étude. Un protocole de potentiels évoqués visuels (PEVs) utilisant des stimuli en couleur et en mouvement a été employé afin d’appréhender les réponses parvo- et magnocellulaires respectivement. Les concentrations d’acide docosahexaénoïque (ADH) ont été mesurées à la naissance à partir du sang de cordon ombilical et au moment du testing, reflétant ainsi les expositions pré- et post-natales. Les relations entre les niveaux sanguins d’ADH et les PEVs ont été examinées à l’aide d’analyses de régression multiples, en tenant compte des contaminants environnementaux et d’autres variables potentiellement confondantes. Aucune association significative n’a été trouvée en ce qui concerne les stimuli de mouvement. Cependant, après ajustement pour les covariables, les concentrations d’ADH à la naissance étaient associées à une latence plus courte des composantes N1 et P1 des PEVs couleur. Notre étude démontre, pour la première fois, des effets bénéfiques de l’exposition prénatale à l’ADH sur le système parvocellulaire à l’âge scolaire. / Fish and sea mammals consumption is an important source of omega-3 fatty acids, known for their beneficial effects on human brain development. Several lines of evidence indicate that omega-3 fatty acids are beneficial especially for the development of the visual system. However, the long-term effect of prenatal exposure to omega-3 fatty acids on human visual development is unknown. This question was addressed using visual evoked potentials (PEVs) to study a cohort of school-age Inuit children (n = 136; mean age = 11.3 years old) from Arctic Quebec (Nunavik) who received high levels of omega-3 intake during gestation. PEV protocols using color and motion-onset stimuli were used to assess the parvocellular and magnocellular responses, respectively. Concentrations of the omega-3 fatty acid DHA were measured at birth in the umbilical cord and at the time of testing, reflecting pre- and post-natal exposure, respectively. Relations between omega-3 and VEPs were assessed by multivariate regression analyses, taking into account environmental contaminants and other potential confounding variables. No significant associations were found with motion-onset VEPs. However, after adjustment for covariables, cord blood concentrations of DHA were associated with a shorter latency of the N1 and P1 components of the color VEPs. Our study suggests beneficial effects of DHA on the visual parvocellular system at school age. This is the first study supporting the longlasting beneficial effects of prenatal exposure to DHA.

The gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) require n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for optimal growth and health. Due to the rapid growth of global aquaculture the quantity of marine oils used in aquafeeds has been limited, yet the overall quantity of oil in an aquafeed has increased by the addition of vegetable oil (VO) to supply dietary energy. For aquaculture to continue to grow more fish must be produced with less marine ingredients, yet EPA and DHA must be maintained at levels above fish requirements. This project set out to re-evaluate the requirement for EPA and DHA in gilthead seabream and European seabass. Two dose-response studies were designed and executed where juvenile seabream and seabass were fed one of six levels of EPA+DHA (0.2 – 3.2 % as fed). Biometric data were collected and analysed to determine new requirement estimates for EPA+DHA for fish of two weight ranges (24 – 80 g and 80 – 200 g). The effects of the dietary LC-PUFA gradient on lipid composition and metabolism were also considered.

Après quelques rappels bibliographiques (biologiques et chimiques) sur les rétinoïdes et sur l'angiogenèse (chapitre I), ce travail décrit, dans un premier temps, la synthèse du composé B2, un analogue du DHA (Acide DocosaHexaènoïque) (chapitre II). Du fait de l'activité rétinoïdienne et anti-angiogénique du DHA, de tels analogues (plus stables que le DHA lui-même) pourraient être intéressants dans le domaine de la lutte contre le cancer. Le chapitre III est consacré à l'étude de plusieurs nouvelles réactions multicomposants palladocatalysées permettant de générer, en une seule étape, deux ou trois liaisons Carbone-Carbone de manière totalement régio- et stéréo-sélective à partir des produits souvent commerciaux que sont les halogénures benzyliques et les alynes terminaux. Ces réactions aboutissent à des produits dont le squelette carboné est de type ényne. Le chapitre IV présente les résultats obtenus pour certains de ces énynes dans quatre tests biologiques. Les tests effectués sont : l'affinité pour les récepteurs des oestrogènes, la modulation de l'activité luciférase dans les cellules MELN, l'activité antileishmannienne et la cytotoxicité. Certains produits présentent des activités encourageantes.

La consommation de poisson et de mammifères marins représente une source importante d’acides gras oméga-3 connus pour leurs effets bénéfiques sur le développement des fonctions cérébrales et notamment, sur le développement du système visuel. Afin de tester l’hypothèse selon laquelle l’exposition prénatale aux acides gras oméga-3 a des effets bénéfiques à long terme, nous avons examiné les fonctions visuelles chez des enfants Inuits d’âge scolaire exposés à de grandes quantités d’oméga-3 durant la période de gestation. Des enfants Inuits (n = 136; moyenne d’âge = 11.3 ans) du nord du Québec (Nunavik) ont participé à cette étude. Un protocole de potentiels évoqués visuels (PEVs) utilisant des stimuli en couleur et en mouvement a été employé afin d’appréhender les réponses parvo- et magnocellulaires respectivement. Les concentrations d’acide docosahexaénoïque (ADH) ont été mesurées à la naissance à partir du sang de cordon ombilical et au moment du testing, reflétant ainsi les expositions pré- et post-natales. Les relations entre les niveaux sanguins d’ADH et les PEVs ont été examinées à l’aide d’analyses de régression multiples, en tenant compte des contaminants environnementaux et d’autres variables potentiellement confondantes. Aucune association significative n’a été trouvée en ce qui concerne les stimuli de mouvement. Cependant, après ajustement pour les covariables, les concentrations d’ADH à la naissance étaient associées à une latence plus courte des composantes N1 et P1 des PEVs couleur. Notre étude démontre, pour la première fois, des effets bénéfiques de l’exposition prénatale à l’ADH sur le système parvocellulaire à l’âge scolaire. / Fish and sea mammals consumption is an important source of omega-3 fatty acids, known for their beneficial effects on human brain development. Several lines of evidence indicate that omega-3 fatty acids are beneficial especially for the development of the visual system. However, the long-term effect of prenatal exposure to omega-3 fatty acids on human visual development is unknown. This question was addressed using visual evoked potentials (PEVs) to study a cohort of school-age Inuit children (n = 136; mean age = 11.3 years old) from Arctic Quebec (Nunavik) who received high levels of omega-3 intake during gestation. PEV protocols using color and motion-onset stimuli were used to assess the parvocellular and magnocellular responses, respectively. Concentrations of the omega-3 fatty acid DHA were measured at birth in the umbilical cord and at the time of testing, reflecting pre- and post-natal exposure, respectively. Relations between omega-3 and VEPs were assessed by multivariate regression analyses, taking into account environmental contaminants and other potential confounding variables. No significant associations were found with motion-onset VEPs. However, after adjustment for covariables, cord blood concentrations of DHA were associated with a shorter latency of the N1 and P1 components of the color VEPs. Our study suggests beneficial effects of DHA on the visual parvocellular system at school age. This is the first study supporting the longlasting beneficial effects of prenatal exposure to DHA.

Introduction Optimal nutrition is vital in the management of infants born preterm. Dietary fat in infancy is fundamental for the provision of energy for growth and development. Essential fatty acids, specifically Long Chain Polyunsaturated Fatty Acids (LC-PUFAs) such as docosahexaenoic acid (DHA), have been under investigation by several international research groups in the past decade. Essential fatty acids are critical in neurodevelopment as DHA is found in high proportions in structural lipids of cell membranes, particularly in the central nervous system (CNS). The accumulation of essential fatty acids and particularly DHA in the brain and retina occurs most rapidly during the perinatal period, therefore preterm infants are of particular concern (Singer, 2001). Current scientific consensus is that the optimum growth rate for preterm infants is equal to the in utero growth rate throughout the last trimester, however, failure to achieve the optimum intrauterine growth rate is common in preterm infants (Olhager and Forsum, 2003). Preterm infants require large amounts of energy and nutrients with which many infants are not provided or are not able to absorb, due to immature gastrointestinal and metabolic systems and other medical complications (Olhager and Forsum, 2003). There are a number of unresolved issues regarding optimal growth rate and total energy requirements (ER) for preterm infants. Hypotheses/Objectives This study is a “side study” to a double blind randomised controlled trial (RCT) of DHA supplementation in preterm infants. The hypothesis of this “side study” is that increased DHA during the neonatal period would increase total energy expenditure (TEE) and improve neurodevelopmental outcome. Specifically, at term postconceptual age (PCA) it was hypothesised that preterm infants receiving higher intake of DHA would have higher TEE’s due to the acceleration in brain maturation. Also, it was hypothesised that preterm infants receiving high levels of DHA would have TEE’s equivalent to term born infants due to their same brain maturation status. Other hypothesised effects of DHA supplementation include an accelerated maturation of the visual cortical pathways, and accelerated white matter (WM) tract development aiding in brain maturation. The first objective of this study was to measure TEE and ER in very preterm infants when they reached an age of 31-33 weeks post conceptional age (PCA). The effects of DHA supplementation on TEE, at simulated in utero levels, in very preterm infants (born < 33 weeks PCA), when assessed at term equivalent (40 weeks PCA) were studied. Another objective was to compare WM brain tissue volume at term PCA between two preterm groups and then with the term born infants. Visual latency was also compared between the two preterm infant groups and then with the term born infants. Methods TEE was measured using the doubly labelled water (DLW) method which is based on the differential elimination of 2H (deuterium) and 18O from the body subsequent to a loading dose of these isotopes. TEE was measured at the preterm age between 31-33 weeks PCA and again at term PCA. TEE measurements are made at term PCA in a term born control group. Brain assessment was by Magnetic Resonance Imaging and (MRI) and Visual Evoked Potential (VEP). Magnetic resonance imaging quantitatively measured brain volumes and WM. Visual evoked potential would provide information on visual latency and amplitude. Results The cohort consisted of 38 infants. The TEE of the very preterm infant group was measured at 31-33 weeks PCA. The mean (±standard deviation) (SD) TEE was calculated at 80(±27) kcal/kg/d, and using data in the literature for foetal energy accretion of 28kcal/kg/d, the mean ER was calculated to be 108(±27) kcal/kg/d. At term PCA TEE was calculated for the preterm DHA supplemented group to be 56(±19) kcal/kg/d and for the non-DHA supplemented group 70(±39) kcal/kg/d. These measurements were not statistically different. Flash VEP conducted on preterm given different amounts of DHA tested at term PCA found no statistically different measurements. When combining these results and comparing them to measurements of term born infants at term PCA, the right eye measurements showed that preterm infants had statistically greater latencies than term infants. When combining the left and right eye measurements the latencies no statistical significance was found. Amplitude was also not statistically significant between the groups. MRI measures at term PCA were not statistically different DHA supplemented and the non-DHA supplemented preterm infant group. When the preterm infant cohort was combined and compared to the term born infant group, the results showed that preterm infants imaged at term PCA had reduced WM development in a number of frontal lobe projections, and anterior and posterior commissarial pathways of the corpus callosum and corona radiata. Discussion The TEE and ER measurements in this study represent the largest preterm infant cohort to date. The ER values reported here are of value in allowing the calculation of appropriate feeding and nutritional strategies for preterm infants. Although no differences in TEE between the DHA and non DHA supplemented groups were found this may have been due to the small sample size. With regard to the latency outcomes, it can be speculated that if measurements were conducted at a later PCA the correlations may have been stronger and significant. Several other factors may have also affected the results, including alertness of the infant at the time of testing, thickness of the cranium, and other health factors could not be controlled for. This study contains the youngest cohort to be compared via Flash VEP. The MRI data did not find significant differences in brain volume and WM between the DHA supplemented and the non-DHA supplemented groups. The infant CNS is rapidly developing and there are multiple environmental factors which may have affected outcomes. The data did however find differences in WM development between the preterm and term infants. The reduced WM development found in the preterm infants compared to term born infants may provide some explanation for the correlation between preterm birth and poorer cognitive and functional outcomes. Larger studies which extend beyond the first months of life are recommended in order to investigate the long-term relationships between DHA supplementation, TEE and brain maturation.

The aim of this study is to analyse the discourse surrounding the preservation of the Icelandic language in light of the growing immigrant population in Iceland. This is done by analysing and comparing two public language policies through the lens of Critical Discourse Analysis, more specifically Discourse Historical Approach. This thesis contributes to the academic research on the Icelandic language and its immigrant population by offering a comparative study of a previously unexplored research topic. The findings indicate that there has been a discursive shift from conservative to more progressive attitudes towards the preservation of the Icelandic language, and the connection between language preservation and purification is beginning to weaken. The study shows that immigrants’ role as language users and language preservers is not sufficiently addressed or met, and a more inclusive approach towards the language is needed to facilitate the prosperous growth of a multicultural society and immigrants’ sense of belonging.

Länge har det funnits en föreställning om att den rasism som riktas mot öst- och sydostasiater är en ”positiv” sådan, eller så har asiater helt enkelt varit frånvarande i anti-rasistiska diskurser. I samband med covid-19 eskalerade hatbrott mot asiater, vilket synliggjorde anti-asiatisk rasism som ett aktuellt samhällsproblem som alltid funnits. I denna uppsats undersöks hur öst- och sydostasiater representeras diskursivt i det svenska internetforumet Flashback i syfte att öka medvetenhet om rasism mot asiater och vidare bidra till att motarbeta de kvarstående ojämlikheterna mellan olika etniska grupper. Studien tar avstamp i ett konstruktivistiskt perspektiv på språk och diskriminering och den kritiska diskursanalysen (CDA) som övergripande analysramverk. Sammanlagt 22 diskussionstrådar som behandlar ämnen som Asien, asiat och de östasiatiska nationerna har analyserats med hjälp av Membership Categorization Analysis (MCA) och den diskurshistoriska analysen (DHA).   Undersökningen utgörs av tre delstudier som ska belysa tre olika aspekter av diskriminering av asiater: 1) kategorisering av asiater; 2) de diskursiva strategier som används av skribenterna för att förneka och rättfärdiga nedsättande kommentarer; 3) diskussioner om den så kallade ”guling-humorn”, det vill säga de rasstereotypiska framställningarna av asiater som präglas av humor och komik. Resultatet visar bland annat hur kategorin asiat tillskrivs högst motsägelsefulla egenskaper och förväntningar, och att kontexten spelar en avgörande roll för att interaktionsdeltagarna ska kunna välja ut de mest relevanta föreställningarna om asiater. Detta påvisar att diskrimineringen av asiater inte enbart är ”positiv” utan kategorin kan ofta förknippas med tydligt negativa värderingar i olika sammanhang. Den andra delstudien har sedan belyst att olika diskursiva strategier kan användas beroende på två sammanhang: när rasism som sådan förnekas och när de enskilda nedvärderande kommentarerna riktade mot asiater rättfärdigas. Förnekandet av rasism förekommer främst i de diskussionsämne som har direkt koppling till det svenska samhället såsom mångkulturalism och invandring, medan nedsättande kommentarer om östasiater framträder mer frekvent i de trådar där de enskilda östasiatiska nationerna står i fokus. I den sista delstudien identifieras de olika diskursiva strategier som skribenterna använder för att förneka den kränkande aspekten hos ”humoristiska” karikatyrer av östasiater, vilket bidrar till att bevara Sveriges positiva självbild som världens mest toleranta och antirasistiska samhälle.

Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) with neuroprotective and cardioprotective properties. It is thought that some of the actions of EPA may be attributed to its elongated metabolite, the PUFA docosapentaenoic acid (DPA). Docosahexaenoic acid (DHA) and arachidonic acid (AA) are bioactive PUFA ubiquitously expressed in neural tissues. EPA and AA can be converted by cyclooxygenase (COX) to prostanoids and by lipoxygenase (LOX) to hydroxy fatty acids. PUFA can also be converted to ethanolamides in the brain. These mediators are involved in physiological and pathological processes in many bodily systems. The purpose of this study was to examine the production of eicosanoids, hydroxy fatty acids and fatty acid ethanolamides in young and aged rat brain following EPA or DPA enriched diets. The effects of specific PUFA on human platelet eicosanoid production were also investigated as these mediators play a role in adhesion and aggregation. Liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) assays were developed and used to measure lipid mediators in rat brain and human platelets. Ageing in rat brain was accompanied with several changes in the prostanoid and hydroxy fatty acid profiles. Supplementing the diet with EPA or DPA at a daily dose of 200 mg/kg for 8 weeks prevented these changes and decreased levels of PGE2. DPA changed the profile of hydroxy fatty acids synthesised in the brain tissue of young animals. This study has shown that levels of eicosapentaenoylethanolamide (EPA-EA) increase in the brain as a result of ageing and that this is accompanied by an increase in levels of anandamide. Feeding aged animals EPA or DPA further increased the levels of EPA-EA but prevented any change in the level of anandamide. Niacin is used to treat hypercholesterolaemia although it is associated with an unpleasant PGD2 mediated skin flush. This exploratory study has shown that human platelets treated with niacin did not show any changes in their prostanoid and hydroxy fatty acid profiles. Platelets treated with EPA showed increased production of TXB3 and 12-HEPE. Niacin augmented the effects of EPA on human platelet mediator synthesis. Overall, this study has demonstrated that EPA can change brain and platelet lipid mediator synthesis and has provided evidence that could explain some of the neuroprotective and cardioprotective actions of this PUFA.

Le récepteur LSR est un acteur important du métabolisme hépatique, puisqu'il joue un rôle dans la clairance des lipoprotéines à ApoB/ApoE riches en triglycérides durant la période postprandiale. Dans cette étude, nous avons montré qu'un traitement in vitro par DHA peut augmenter les niveaux de protéine et d'activité LSR dans les cellules d'hépatome de souris Hepa 1-6. En toute cohérence, un régime supplémenté en DHA a conduit à élever les niveaux de protéine LSR hépatique chez la souris. Mais aucune de ces deux études n'a montré de changement au niveau des ARNm. Ceci suggère que l'enrichissement en DHA influe positivement sur le microenvironnement de LSR et son ancrage à la surface de la cellule. Nous avons ensuite étudié le rôle du récepteur PPAR[alpha] dans la régulation du gène lsr. Une analyse in silico nous a permis d'identifier des éléments PPRE dans la région 5' régulatrice du gène humain et de ses homologues de souris et de rat. Des traitements pharmacologiques par des agoniste et antagoniste spécifiques de PPAR[alpha] ont montré que ce récepteur est impliqué dans la régulation transcriptionnelle de l'expression du LSR dans les cellules Hepa 1 6. Enfin, une analyse transcriptomique a révélé une diminution de l'expression de PPAR[alpha] et d'autres gènes impliqués dans le métabolisme lipidique hépatique chez la souris LSR+/- sous régime standard ou riche en graisses. En conclusion, toutes ces études indiquent que l'activité LSR hépatique est sous le contrôle de facteurs nutritionnels capables d'activer divers mécanismes de régulation, faisant du LSR une cible d'intérêt potentiel pour des stratégies nutritionnelles ou thérapeutiques destinées à prévenir ou traiter les dyslipidémies / Lipolysis stimulated lipoprotein receptor (LSR) plays an important role in the clearance of ApoB/ApoE containing triglyceride-rich lipoproteins during postprandial phase. In this study, we demonstrated that in vitro treatment of mouse hepatoma cells, Hepa 1-6, with docosahexaenoic acid (DHA) led to an increase in LSR protein levels as well as its activity. Furthermore, the mice placed on the diet supplemented with DHA showed an increase in hepatic LSR protein. However, the mRNA levels remained unchanged in both in vitro and in vivo studies, suggesting that DHA enrichment may result in changes in LSR microenvironment that could affect its anchorage at the surface of cell membrane. Specific peroxisome proliferator response elements were identified in the upstream region of human, mouse and rat lsr gene by in silico analysis. We therefore sought to determine the role of the transcription factor, peroxisome proliferator-activated receptor (PPAR[alpha]), in LSR regulation. In vitro pharmacological studies using PPAR[alpha]-selective agonist and antagonist agents demonstrated that PPAR[alpha] is indeed involved in the transcriptional regulation of LSR expression. Furthermore, qPCR array analysis revealed the downregulation of PPAR[alpha] and various genes involved in hepatic lipid metabolism in LSR+/- mice on standard and high-fat diets. In conclusion, these studies show that the hepatic LSR activity is controlled by dietary factors that can activate various pathways involved in regulating lipid homeostasis, therefore representing LSR as a potential target for either nutritional or therapeutic strategies towards the prevention or treatment of dyslipidemia