Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2018-11-23T15:19:44Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Roberto Carlos Doring Wolter.pdf: 2034054 bytes, checksum: d53dff149845c79db461dd69fc6b8806 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-11-23T18:52:35Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Roberto Carlos Doring Wolter.pdf: 2034054 bytes, checksum: d53dff149845c79db461dd69fc6b8806 (MD5) / Made available in DSpace on 2018-11-23T18:52:35Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Roberto Carlos Doring Wolter.pdf: 2034054 bytes, checksum: d53dff149845c79db461dd69fc6b8806 (MD5) Previous issue date: 2014-08-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / A toxidez por ferro é um dos mais importantes estresses abióticos em solos de várzea. Depois do surgimento dos sintomas de toxidez na lavoura, apenas medidas paliativas podem ser tomadas para diminuir o efeito do problema. Os objetivos do trabalho foram verificar se os critérios de interpretação para prognóstico do risco de ocorrência da toxidez por ferro em arroz irrigado por alagamento baseado na porcentagem de saturação da CTC por Fe2+ (PSFe2+), que é calculada a partir da estimativa do ferro trocável, proveniente da determinação do ferro extraído por oxalato de amônio pH 6,0 de uma amostra coletada anterior ao alagamento, são válidos para um grupo de solos de várzea do Rio Grande do Sul. Além disso, se a inclusão de outras variáveis melhora a estimação e o prognóstico, e ainda se a relação das classes de riscos está de acordo com a ocorrência da toxidez nas plantas. Para isso foram conduzidos quatro experimentos com plantas usando diferentes solos em casa de vegetação e um experimento em solução nutritiva em laboratório. Os resultados do experimento em solução nutritiva mostram que o surgimento dos sintomas de toxidez por ferro nas plantas de arroz apenas ocorreram a partir da fração entre 0,45 e 0,60 de ferro pelos cátions divalentes, diferente do valor de 0,40 da fração de ferro na solução definido como crítico para a toxidez pelo método, no entanto, não foi detectada mudança nos teores de ferro no tecido das plantas quando se variou a fração molar de ferro na solução nutritiva. Com os resultados dos experimentos com plantas em solos verificou-se que a alta PSFe2+ de uma amostra de solo está relacionada a uma maior probabilidade de ocorrência de toxidez por ferro, e em amostra com baixa PSFe2+ quase não ocorrem sintomas de toxidez por ferro, indicando que o método foi eficiente para prever a ocorrência de sintomas de toxidez por ferro nas plantas de arroz, para o grupo de solos. Também foi constatado que o uso das variáveis: C orgânico, ferro e manganês extraídos por oxalato de amônio pH 6 melhora a exatidão da estimação do ferro trocável comparado a estimação apenas pela extração de ferro, porém, isso não se refletiu em melhores prognósticos do risco de ocorrência de toxidez por ferro nas plantas de arroz do grupo de solos estudados, observou-se que as correlações com as duas formas de estimativas de ferro trocável com os atributos relacionados com a toxidez por ferro tiveram coeficientes bem próximos, impossibilitando a definição do melhor método. Pelo menor número de variáveis a serem determinadas, ou seja, pela maior facilidade de execução, a estimação do ferro trocável obtido apenas pelo ferro extraído por oxalato de amônio pH 6,0 é o método mais eficiente para prognosticar o risco de ocorrência de toxidez por ferro para o arroz irrigado. / The iron toxicity is one of the most important abiotic stress in lowland soils. After the appearance of toxicity symptoms in the field, only palliative measures can be taken to lessen the effect of the problem. The aims of this work were to verify if the interpretation criteria for predicting the risk of iron toxicity occurrence in rice plants by flooding based on the percentage saturation of CEC by Fe2+ (PSFe2+), which is calculated from the estimated exchangeable iron from the determination of iron extracted by ammonium oxalate pH 6.0 in a sample collected prior to flooding, are valid for a group of lowland soils from of Rio Grande do Sul. Furthermore, if the inclusion of other variables improves the estimation and prognosis, and if the relation of the classes of risks is consistent with the occurrence of toxicity in plants. For this, four experiments were conducted with plants, using different soils in a greenhouse and an experiment in nutrient solution in laboratory. The results of the experiment in nutrient solution have shown that the emergence of symptoms of iron toxicity in rice plants occurred only for the 0.45 and 0.60 molar ratio of iron to divalent cations, different from the 0.40 molar ratio of iron in solution defined as critical to the toxicity by the method. However, no change was detected for the iron levels on plant tissue when varying the molar ratio of iron in the nutrient solution. With the results of experiments with plants in soil one could verify that the higher the PSFe2+ of a soil sample the greater the probability of toxicity by iron, and for samples with low PSFe2+ almost no symptoms of toxicity occurred, indicating that the method was efficient in predicting the occurrence of iron toxicity symptoms in rice plants, for the group of soils. It was also found that the use of the variables: organic C, iron and manganese extracted by ammonium oxalate pH 6 improve the accuracy of the exchangeable iron estimation, when compared to estimating only by the iron extraction. However, it was not reflected in better prognostic of the risk of iron toxicity occurrence in rice plants, for the group of soils. It was observed that the correlations with the two forms of estimating exchangeable iron-related attributes of toxic iron coefficients were very close, making impossible the definition of the best method. By the small number of variables to be determined, ie, by the easiness of implementation, the estimation of exchangeable iron obtained only by the iron extracted by ammonium oxalate pH 6.0 is the most efficient method to predict the risk of iron toxicity for rice crop. Keywords: symptoms of iron toxicity, molar ratio of iron, iron oxalate, percentage of CEC saturation by Fe2+.

<p>Degradation of the mRNA 3'-end located poly(A) tail is an important step for mRNA decay in mammalian cells. Thus, to understand mRNA decay in detail, it is important to identify the catalytic activities involved in degrading poly(A). We identified and purified a 54-kDa polypeptide responsible for poly(A)-specific 3' exonuclease activity in calf thymus extracts. The 54-kDa polypeptide is a proteolytic fragment of the poly(A)-specific ribonuclease (PARN) 74-kDa polypeptide. PARN is a divalent metal ion dependent, poly(A)-specific, oligomeric, processive and cap interacting 3' exonuclease. An active deadenylation complex, consisting of the poly(A)-tailed RNA substrate and PARN, has been identified. The interaction with the 5'-end cap structure stimulates PARN activity and also amplifies the processivity of the deadenylation reaction. Furthermore, the cap binding site and the active site of PARN are separate from each other. To characterise the active site of PARN, we per-formed side-directed mutagenesis, Fe²⁺-mediated hydroxyl radical cleavage and metal ion switch experiments. We have demonstrated that the conserved acidic amino acid residues D28, E30, D292 and D382 of human PARN are essential for PARN activity and that these amino acid residues are directly involved in the co-ordination of at least two metal ions in the active site of PARN. Phosphorothioate modification on RNA substrates revealed that the pro-R oxygen atom of the scissile phosphate group interacts directly with the metal ion(s). Based on our studies, we propose a model for the action of PARN. Similarly to what has been observed for ribozymes, aminoglycoside antibiotics inhibit PARN activity, most likely by the displacement of catalytically important divalent metal ions. Among the aminoglycoside antibiotics tested, neomycin B is the most potent inhibitor. We speculate that inhibition of enzymes using similar catalytic mechanisms as PARN could be a reason for the toxic side effects caused by aminoglycoside antibiotics in clinical practice. </p>

Degradation of the mRNA 3'-end located poly(A) tail is an important step for mRNA decay in mammalian cells. Thus, to understand mRNA decay in detail, it is important to identify the catalytic activities involved in degrading poly(A). We identified and purified a 54-kDa polypeptide responsible for poly(A)-specific 3' exonuclease activity in calf thymus extracts. The 54-kDa polypeptide is a proteolytic fragment of the poly(A)-specific ribonuclease (PARN) 74-kDa polypeptide. PARN is a divalent metal ion dependent, poly(A)-specific, oligomeric, processive and cap interacting 3' exonuclease. An active deadenylation complex, consisting of the poly(A)-tailed RNA substrate and PARN, has been identified. The interaction with the 5'-end cap structure stimulates PARN activity and also amplifies the processivity of the deadenylation reaction. Furthermore, the cap binding site and the active site of PARN are separate from each other. To characterise the active site of PARN, we per-formed side-directed mutagenesis, Fe2+-mediated hydroxyl radical cleavage and metal ion switch experiments. We have demonstrated that the conserved acidic amino acid residues D28, E30, D292 and D382 of human PARN are essential for PARN activity and that these amino acid residues are directly involved in the co-ordination of at least two metal ions in the active site of PARN. Phosphorothioate modification on RNA substrates revealed that the pro-R oxygen atom of the scissile phosphate group interacts directly with the metal ion(s). Based on our studies, we propose a model for the action of PARN. Similarly to what has been observed for ribozymes, aminoglycoside antibiotics inhibit PARN activity, most likely by the displacement of catalytically important divalent metal ions. Among the aminoglycoside antibiotics tested, neomycin B is the most potent inhibitor. We speculate that inhibition of enzymes using similar catalytic mechanisms as PARN could be a reason for the toxic side effects caused by aminoglycoside antibiotics in clinical practice.

Giant magnetostrictive RFe2 type (R represents rare earths) intermetallics form an important class of magnetic materials keeping in view of their potential applications as sensors and/ or actuators. In this thesis, one such mixed rare earth compound (Tb,Dy)Fe2 has been chosen for investigations. Being a technologically important material system, several investigations concerning physical and magnetic properties of the material and effect of processing parameters on magnetic properties have been reported in the available literature. However, existing literature does not provide a clear insight into some important aspects such as phase equilibria, evolution of texture and microstructure of directionally solidified Tb-Dy-Fe alloys. Therefore, the present work was undertaken to bring out tangible process-structure-property correlations with an emphasis to clarify the grey areas in the available literature. The investigation on the nature of ternary phase equilibria of Tb-Dy-Fe was taken up with an aim to understand the effect of Tb/Dy ratio on phase equilibria and magnetic properties of TbxDy1-xFe1.95 (x=0-1) alloys. Microstructural and micro-chemical analysis along with study of lattice parameter has been used to predict the nature of phase equilibria and the deviation from the assumed pseudo-binary behaviour. Further, from the microstructural investigations and study of lattice parameter and Curie temperature, a schematic sketch of a section of the ternary diagram, where (Tb,Dy) / Fe =1.95, was formulated and presented. Directional solidification technique is the most widely adopted method for processing the (Tb,Dy)Fe2, to impart grain orientation for practical applications. Therefore, it was aimed in the present study to understand the evolution of texture and microstructure in directionally solidified Tb0.3Dy0.7Fe1.95 alloy by modified Bridgman and zone melting techniques. The alloy was directionally solidified by modified Bridgman technique with a series of growth rates 5 - 100 cm/h, at a constant temperature gradient of 150oC/ cm. Microstructural investigation revealed formation of island banding at lower growth rate and peritectic coupled growth at higher growth rates. The texture study indicated a transition of growth texture from <113> to <110> and finally to <112> with increase of growth rate. A mechanism based on atomic attachment kinetics is proposed to explain the orientation selection with growth rate. The texture and microstructure have been correlated with magnetostriction and static strain co-efficient (dλ/dH) of the Bridgman solidified alloys. The solidification morphology observed in Bridgman solidified samples was found to be mostly plane front. Therefore, in order to understand the microstructure and texture evolution in cellular/ dendritic regime, directional solidification of Tb0.3Dy0.7Fe1.95 was attempted by zone melting technique with a lesser temperature gradient of 100oC/cm. A detailed texture study indicated a transition in preferred growth direction from <110> to <112> with increase of growth rate. In this case of cellular/ dendritic growth regime, a mechanism based on atomic attachment kinetics has been proposed and the preferred morphologies of the solid-liquid interface for <110> and <112> growth have been modelled. The modelled interfaces have been correlated to the shape of cell/ dendrite cross-section observed for the growth rates adopted in this study. Apart from the investigation carried out on the (Tb,Dy)Fe2 alloys, attempts have been made to understand the role of microstructure, especially the ordered phases on the magnetostriction of an emerging magnetostrictive material Fe-Ga. A series of alloy compositions of Fe-x at % Ga (x=17, 20, 23 and 25) were prepared and subjected to different thermal treatments and characterized for microstructural features and magnetostriction. Microstructure investigation of slow cooled, quenched and quenched + aged alloys reveals formation of ordered DO3 phase from disordered A2 phase by first order transformation in 17 and 20 at% Ga alloys, whereas for 23 and 25 at% alloys, the transformation takes place by continuous ordering. It could be observed that large magnetostriction arises owing to the presence of disordered A2 phase or ordered DO3 phase alone. The magnetostriction however decreases substantially when these two phases are co-existing.

Dans cette thèse, des techniques d’homogénéisation multi-échelles sont proposées pour l’analyse des vibrations des matériaux composites viscoélastiques. Dans la première partie, la Méthode Asymptotique à Deux Echelles (MADE) est proposée pour la modélisation des vibrations des longues structures sandwichs viscoélastiques répétitives. Pour ce type de structures les pulsations amorties correspondant aux modes propres de vibration sont regroupées en paquets bien distincts. La MADE décompose le problème initial de grande taille en deux problèmes de petites tailles. Le premier est défini sur quelques cellules de base et le second est une équation différentielle d’amplitude à coefficients complexes. La résolution de ces problèmes permet de déterminer les propriétés amortissantes correspondant aux modes de début et de fin de paquet de la structure tout en évitant la discrétisation de toute la structure. Pour les structures dont les coeurs ont un module d’Young dépendant de la fréquence, le problème non linéaire formulé sur les cellules de bases est résolu par l’approche diamant. Les modèles ADF et à dérivées fractionnaires ont été considérés dans les tests numériques. En utilisant la MADE, on évite la discrétisation de toute la structure, ce qui permet donc de réduire considérablement le temps de calcul ainsi que l’espace mémoire CPU nécessaires. L’approche proposée a été validée en comparant les résultats à ceux de la simulation éléments finis basée sur la discrétisation de toute la structure, et utilisant l’approche diamant. Dans la seconde partie de cette thèse, la méthode des éléments finis multi-échelles (EF2) a été développée pour le calcul des propriétés modales des structures à matériaux hétérogènes viscoélastiques en terme de fréquences amorties et amortissements modaux. Dans le principe de l’approche EF2, le problème de vibration est formulé à deux échelles : l’échelle de la structure globale (échelle macroscopique) et l’échelle d’un VER minutieusement choisi (échelle microscopique). Le problème à résoudre à l’échelle microscopique est un problème non linéaire alors que le problème à résoudre à l’échelle macroscopique est un problème linéaire. La non linéarité à l’échelle microscopique est introduite par la dépendance en fréquence du module d’Young des matériaux des phases viscoélastiques. Le problème non linéaire ainsi généré à l’échelle microscopique est résolu grâce à la MAN et ses outils de différentiation automatique réalisés sous Matlab, Fortran et C++. Un outil numérique, générique, robuste, peu coûteux en temps de calcul et espace mémoire CPU, de résolution des problèmes de vibrations non amorties des structures composites viscoélastique est ainsi mis en place. Le modèle viscoélastique à module constant ainsi que des modèles à modules dépendant de la fréquence notamment le modèle ADF et le modèle à dérivées fractionnaires ont été considérés pour les tests numériques de validation. Les comparaisons avec les résultats ABAQUS ont confirmé l’efficacité du code propos é. Le modèle est ensuite utilisé pour le calcul des propriétés amortissantes des structures sandwichs viscoélastiques à coeur composite. Les capacités de la nouvelle approche à concevoir des structures sandwichs viscoélastiques à coeur composite et à haut pouvoir amortissant ont été testées avec succès à travers l’étude de l’influence des différents paramètres des inclusions sur les propriétés amortissantes d’une structure sandwich viscoélastique à coeur composite / In this thesis, multiscale homogenization techniques are proposed for vibration analysis of structures with viscoelastic composite materials. In the first part, the Double Scale Asymptotic Method is proposed for vibration modeling of large repetitive viscoelastic sandwich structures. For this kind of structures, la eigenfrequencies are closely located in well separated packets. The DSAM splits the initial problem of large size into two problems of relatively small sizes. The first problem is posed on few basic cells, and the second one is an amplitude equation with complex coefficients. The resolution of these equations permits to compute the damping properties that correspond to the beginning and the end of every packets of eigenmodes. In case of structure with frequency dependent Young modulus in the core, the diamant approach is used to solve the nonlinear problem posed on basic cells. The ADF and fractional derivative models are considered in numerical tests. By using the DSAM, one avoid the discretization of the whole structure, and the computation time and needed CPU memory are thus reduced. The proposed method is validated by comparing its results with those of the direct finite element method using the diamant approach. In the second part of this thesis, the multiscale finite element method (FE2) is proposed for computation of modal properties (resonant frequency and modal loss factors) of structures with composite materials. In the principle of the (FE2) method, the vibration problem is formulated at two scales: the scale of the whole structure (macroscopic scale) and the scale of a Representative Volume Element (RVE) considered as the microscopic scale. The microscopic problem is a nonlinear one and the macroscopic problem is linear. The nonlinearity at the microscopic scale is introduced by the frequency dependence of the Young modulus of the viscoelastic phases. This nonlinear problem is solved by the Asymptotic Numerical Method and its automatic differentiation tools realizable in Matlab, Fortran or C++. From this approach, numerical tool that is generic, flexible, robust and inexpensive in term of CPU time and memory is proposed for vibration analysis of viscoelastic structures. The constant Young modulus and frequency dependent Young modulus are considered in validation tests. The results of numerical simulation with ABAQUS are used are reference. The model is then used to compute the modal properties of sandwich structure with viscoelastic composite core. To test the capacities of the proposed approach to design sandwich viscoelastic structure with high damping properties, the influence of parameters of the inclusions are studied

Background Iron deficiency (ID) is the world‟s most prevalent micronutrient deficiency and predominantly affects developing countries, also South Africa. In areas with low fish consumption and high n-6 PUFA vegetable oil intake, there is a risk for having inadequate n-3 PUFA status. Both iron and n-3 PUFA play important roles in the immune response, and supplementation is a strategy to alleviate deficiencies. However, little is known about potential interactive effects between concurrent iron and n-3 PUFA supplementation on the immune system. This is also important in the context that iron supplementation may be unsafe and may increase morbidity and mortality. Aim The overall aim of this thesis was to assess the effects of iron and docosahexaenoic (DHA)/eicosapentaenoic acid (EPA) supplementation, alone and in combination, on the immune system of ID children. More specifically, these effects were investigated on the occurrence and duration of illness and school-absenteeism due to illness, peripheral blood mononuclear cell (PBMC), red blood cell (RBC) and plasma total phospholipid fatty acid composition, iron status, fatty acid-derived immune modulators and targeted PBMC gene expression. Furthermore, association of PBMC, RBC and plasma total phospholipid fatty acid composition with allergic disease, were also examined. Design In a 2-by-2 factorial, randomised, double-blind, placebo-controlled trial, South African children (n = 321, aged 6–11 y) were randomly assigned to receive oral supplements of either 1) iron (50 mg as ferrous sulphate) plus placebo; 2) DHA/EPA (420/80 mg) plus placebo; 3) iron plus DHA/EPA (420/80 mg); or 4) placebo plus placebo for 8.5 mo, four times per week. Absenteeism and illness symptoms were recorded and biochemical parameters for compliance as well as parameters fundamental to immune function were assessed at baseline and endpoint. Furthermore, in a cross-sectional design, associations of allergic disease with baseline fatty acid composition of PBMC, RBC and plasma were examined. Results The combination of iron and DHA/EPA significantly attenuated respiratory illness caused by iron supplementation. DHA/EPA supplementation alone improved respiratory symptoms at school, but increased headache-related absenteeism. DHA/EPA and iron supplementation individually tended to increase and decrease anti-inflammatory DHA and EPA-derived mediators, respectively. Furthermore the anti-inflammatory DHA-derived immune mediator, 17HDHA was higher in the DHA/EPA plus placebo and iron plus DHA/EPA groups than in the iron plus placebo group. Also, the pro-inflammatory arachidonic acid (AA)-derived modulators (5- and 15-hydroxyeicosapentaenoic acid) were significantly lower in the iron plus DHA/EPA group compared to the placebo plus placebo groups. In the study population, 27.2% of the children had allergic disease and AA in PBMC phospholipids was significantly lower in the allergic children than in the non-allergic children. In RBC phospholipids dihomo-gamma-linolenic acid (DGLA) and the ratio of DGLA: linoleic acid (LA) correlated negatively and the n-6:n-3 PUFA ratio positively with total immunoglobulin E (tIgE). Furthermore, trans-C18:1n-9, tended to be higher in the allergic group. Conclusion DHA/EPA prevented respiratory illness caused by iron supplementation and although DHA/EPA on its own reduced respiratory morbidity when the children were present at school, surprisingly it increased the likelihood of being absent with headache and fever. The biochemical findings compliment the clinical results and support previous observations about DHA/EPA supplementation to reduce inflammation, but add to the current knowledge base that a relatively high oral dose of non-haem iron modulates circulating lipid-derived immune modulators and related gene expression. Furthermore, when supplementing with iron and DHA/EPA combined, in this ID population with low fish intake, the anti-inflammatory effect of DHA/EPA is maintained concurrently with attenuation of respiratory morbidity. This finding support the notion that excess iron (probably as non-transferrin bound iron) becomes available for pathogens and is probably why we found that iron increased respiratory infectious morbidity. The improved clinical outcome with combined supplementation seems to be related to increased lipid-mediator synthesis gene expression and the availability of DHA/EPA, leading to a more pro-resolving profile and enhanced immune competence. Overall these results give better insight into immune function and infectious morbidity in relation to n-3 PUFA and iron status and treatment, as well as the possible association of fatty acid status with allergic disease in young South-African school children. / PhD (Nutrition), North-West University, Potchefstroom Campus, 2015

Background Iron deficiency (ID) is the world‟s most prevalent micronutrient deficiency and predominantly affects developing countries, also South Africa. In areas with low fish consumption and high n-6 PUFA vegetable oil intake, there is a risk for having inadequate n-3 PUFA status. Both iron and n-3 PUFA play important roles in the immune response, and supplementation is a strategy to alleviate deficiencies. However, little is known about potential interactive effects between concurrent iron and n-3 PUFA supplementation on the immune system. This is also important in the context that iron supplementation may be unsafe and may increase morbidity and mortality. Aim The overall aim of this thesis was to assess the effects of iron and docosahexaenoic (DHA)/eicosapentaenoic acid (EPA) supplementation, alone and in combination, on the immune system of ID children. More specifically, these effects were investigated on the occurrence and duration of illness and school-absenteeism due to illness, peripheral blood mononuclear cell (PBMC), red blood cell (RBC) and plasma total phospholipid fatty acid composition, iron status, fatty acid-derived immune modulators and targeted PBMC gene expression. Furthermore, association of PBMC, RBC and plasma total phospholipid fatty acid composition with allergic disease, were also examined. Design In a 2-by-2 factorial, randomised, double-blind, placebo-controlled trial, South African children (n = 321, aged 6–11 y) were randomly assigned to receive oral supplements of either 1) iron (50 mg as ferrous sulphate) plus placebo; 2) DHA/EPA (420/80 mg) plus placebo; 3) iron plus DHA/EPA (420/80 mg); or 4) placebo plus placebo for 8.5 mo, four times per week. Absenteeism and illness symptoms were recorded and biochemical parameters for compliance as well as parameters fundamental to immune function were assessed at baseline and endpoint. Furthermore, in a cross-sectional design, associations of allergic disease with baseline fatty acid composition of PBMC, RBC and plasma were examined. Results The combination of iron and DHA/EPA significantly attenuated respiratory illness caused by iron supplementation. DHA/EPA supplementation alone improved respiratory symptoms at school, but increased headache-related absenteeism. DHA/EPA and iron supplementation individually tended to increase and decrease anti-inflammatory DHA and EPA-derived mediators, respectively. Furthermore the anti-inflammatory DHA-derived immune mediator, 17HDHA was higher in the DHA/EPA plus placebo and iron plus DHA/EPA groups than in the iron plus placebo group. Also, the pro-inflammatory arachidonic acid (AA)-derived modulators (5- and 15-hydroxyeicosapentaenoic acid) were significantly lower in the iron plus DHA/EPA group compared to the placebo plus placebo groups. In the study population, 27.2% of the children had allergic disease and AA in PBMC phospholipids was significantly lower in the allergic children than in the non-allergic children. In RBC phospholipids dihomo-gamma-linolenic acid (DGLA) and the ratio of DGLA: linoleic acid (LA) correlated negatively and the n-6:n-3 PUFA ratio positively with total immunoglobulin E (tIgE). Furthermore, trans-C18:1n-9, tended to be higher in the allergic group. Conclusion DHA/EPA prevented respiratory illness caused by iron supplementation and although DHA/EPA on its own reduced respiratory morbidity when the children were present at school, surprisingly it increased the likelihood of being absent with headache and fever. The biochemical findings compliment the clinical results and support previous observations about DHA/EPA supplementation to reduce inflammation, but add to the current knowledge base that a relatively high oral dose of non-haem iron modulates circulating lipid-derived immune modulators and related gene expression. Furthermore, when supplementing with iron and DHA/EPA combined, in this ID population with low fish intake, the anti-inflammatory effect of DHA/EPA is maintained concurrently with attenuation of respiratory morbidity. This finding support the notion that excess iron (probably as non-transferrin bound iron) becomes available for pathogens and is probably why we found that iron increased respiratory infectious morbidity. The improved clinical outcome with combined supplementation seems to be related to increased lipid-mediator synthesis gene expression and the availability of DHA/EPA, leading to a more pro-resolving profile and enhanced immune competence. Overall these results give better insight into immune function and infectious morbidity in relation to n-3 PUFA and iron status and treatment, as well as the possible association of fatty acid status with allergic disease in young South-African school children. / PhD (Nutrition), North-West University, Potchefstroom Campus, 2015