14 research outputs found

    Investigation of type-pi 2 geomagnetic pulsations at magnetoconjugate points

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    Type pi2 geomagnetic pulsations and Alfven wave resonance on night side of magnetospher

    Lutein and zeaxanthin attenuates VEGF-induced neovascularisation in human retinal microvascular endothelial cells through a Nox4-dependent pathway

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    Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are two of the most common and severe causes of vision loss in the population. Both conditions are associated with excessive levels of vascular endothelial growth factor (VEGF) in the eye which results in an increase in the formation of new blood vessels through a process called neovascularisation. As such, anti-VEGF therapies are currently utilised as a treatment for patients with AMD however they are associated with painful administration of injections and potential degeneration of healthy endothelium. There is therefore growing interest in alternate treatment options to reduce neovascularisation in the eye. The use of carotenoids, lutein (L) and zeaxanthin (Z), has been shown to improve vision loss parameters in patients with AMD, however the underlying mechanisms are not well-understood. We studied the impact of these compounds on neovascularisation processes using an in vitro cell model of the retinal microvascular endothelium. Our findings show that L and Z reduced VEGF-induced tube formation whilst, in combination (5:1 ratio), the compounds significantly blocked VEGF-induced neovascularisation. The carotenoids, individually and in combination, reduced VEGF-induced oxidative stress concomitant with increased activity of the NADPH oxidase, Nox4. We further demonstrated that the Nox4 inhibitor, GLX7013114, attenuated the protective effect of L and Z. Taken together, these findings indicate the protective effect of the carotenoids, L and Z, in reducing VEGF-mediated neovascularisation via a Nox4-dependent pathway. These studies implicate the potential for these compounds to be used as a therapeutic approach for patients suffering from AMD and proliferative DR

    Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium

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    Background: One of the most prevalent microvascular complications for patients with diabetes is diabetic retinopathy (DR) associated with increased retinal endothelial blood vessel formation. Treatments to reduce vascularisation in the retinal endothelium are linked to improved sight in patients with DR. Recently we have demonstrated the novel protective role of the artificial sweetener, sucralose, and the sweet taste receptor, T1R3, in the pulmonary endothelium to reduce vascular leak. In the present study, we examined the role of sucralose and sweet taste receptors on vasculogenic processes (proliferation, migration, adhesion and tube formation) in a cell model of the retinal endothelium . Methods: We exposed human retinal microvascular endothelial cells (RMVEC) to VEGF as an in vitro model of DR in the presence and absence of T1R3 agonist sucralose. Results: In RMVEC, we observed increased VEGF-induced cell proliferation, migration, adhesion and tube formation, which was significantly attenuated by exposure to the artificial sweetener sucralose. Following siRNA knockdown of the sweet taste receptor, T1R3, but not T1R2, the protective effect of sucralose on VEGF-induced RMVEC vasculogenic processes was blocked. We further demonstrate that sucralose attenuates VEGF-induced Akt phosphorylation to protect the retinal microvasculature. Conclusion: These studies are the first to demonstrate a protective effect of an artificial sweetener, through the sweet taste receptor T1R3, on VEGF-induced vasculogenesis in a retinal microvascular endothelial cell line

    Impact of epidemiologically identified mixtures of endocrine disrupting chemicals on metabolic programming

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    We are ubiquitously exposed to a plethora of endocrine-disrupting chemicals (EDCs), i.e. substances that alter the function(s) of the endocrine system. While ample evidence show individual EDC's influence on developmental processes resulting in adverse health outcomes, less is known about the effects of human-relevant EDC mixtures exposure. Additionally, there is a lack of appropriate methodology to assess the hazard and risk of complex mixtures. This doctoral project aimed to examine the effects of two EDC mixtures and to compare individual components to its mixture, on the developing metabolic system. And to investigate additivity approach for predicting effects of complex mixtures.  Studied EDC mixtures (G and G1) were previously identified using Swedish Environmental Longitudinal Mother and Child Asthma and Allergy (SELMA) study data, based on their association with lower birth weight. In this thesis, these mixtures, and mixture G1’s components, were tested for effects on adipogenesis and underlying epigenetic and transcriptional changes in human mesenchymal stem cells (hMSCs) and on metabolic rate in zebrafish larvae. In hMSCs, both mixtures induced adipogenesis at concentrations corresponding to SELMA cohort measured levels. Mixture G induced early transcriptional changes of over 1000 genes in a dose-dependent manner. These genes significantly overlapped with glucocorticoid-regulated genes and were involved in early osteogenesis. Mixture G1 induced significant DNA methylation changes at 713 positions and in six genomic regions in genes whose expression or methylation was previously associated with obesity or MSC differentiation. In zebrafish larvae, mixture G1 increased oxygen consumption rate. Compared to mixture G1, none of its individual components showed equally large effects on adipogenesis or metabolic rate. However, mixture G1 effect on both endpoints could be adequately predicted by the additivity model using experimental data from its constituents. In conclusion, this doctoral project showed that mixtures corresponding to human real-life exposures, in terms of proportions and concentrations, can induce molecular, cellular, and whole-organism changes relevant to developmental metabolic programming, which could underlie adverse outcomes later in life. The results emphasise that mixtures matter and should be accounted for in regulatory risk assessments, and provide support for additivity models as a pragmatic approach to mixture risk assessment

    Impact of epidemiologically identified mixtures of endocrine disrupting chemicals on metabolic programming

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    We are ubiquitously exposed to a plethora of endocrine-disrupting chemicals (EDCs), i.e. substances that alter the function(s) of the endocrine system. While ample evidence show individual EDC's influence on developmental processes resulting in adverse health outcomes, less is known about the effects of human-relevant EDC mixtures exposure. Additionally, there is a lack of appropriate methodology to assess the hazard and risk of complex mixtures. This doctoral project aimed to examine the effects of two EDC mixtures and to compare individual components to its mixture, on the developing metabolic system. And to investigate additivity approach for predicting effects of complex mixtures.  Studied EDC mixtures (G and G1) were previously identified using Swedish Environmental Longitudinal Mother and Child Asthma and Allergy (SELMA) study data, based on their association with lower birth weight. In this thesis, these mixtures, and mixture G1’s components, were tested for effects on adipogenesis and underlying epigenetic and transcriptional changes in human mesenchymal stem cells (hMSCs) and on metabolic rate in zebrafish larvae. In hMSCs, both mixtures induced adipogenesis at concentrations corresponding to SELMA cohort measured levels. Mixture G induced early transcriptional changes of over 1000 genes in a dose-dependent manner. These genes significantly overlapped with glucocorticoid-regulated genes and were involved in early osteogenesis. Mixture G1 induced significant DNA methylation changes at 713 positions and in six genomic regions in genes whose expression or methylation was previously associated with obesity or MSC differentiation. In zebrafish larvae, mixture G1 increased oxygen consumption rate. Compared to mixture G1, none of its individual components showed equally large effects on adipogenesis or metabolic rate. However, mixture G1 effect on both endpoints could be adequately predicted by the additivity model using experimental data from its constituents. In conclusion, this doctoral project showed that mixtures corresponding to human real-life exposures, in terms of proportions and concentrations, can induce molecular, cellular, and whole-organism changes relevant to developmental metabolic programming, which could underlie adverse outcomes later in life. The results emphasise that mixtures matter and should be accounted for in regulatory risk assessments, and provide support for additivity models as a pragmatic approach to mixture risk assessment

    Promoting Reading Skills of 5-6 Years Old Children In The Preschool

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    Kvalifikācijas darba temats: “5-6 gadīgu bērnu lasītprasmes veicināšana pirmsskolā”. Pētījuma mērķis: pētīt un analizēt lasītprasmes veicinošus faktorus 5-6 gadīgiem bērniem. Pētījums sastāv no 2 nodaļām un 10 apakšnodaļām. Pētījuma 1. nodaļa tiek izskatīta 5-6 gadīgu bērnu vispārēja attīstība, lasītprasmes veidošana, pedagogu un psihologu atziņas par to. Pētījuma 2. nodaļa veltīta bērnu lasītprasmes veidošanas procesiem. Tajā izskatītā bērnu gatavība lasītprasmes veicināšanai, pētnieku domas par divvalodību, ka arī gatavību lasītprasmes veicināšanai. Pētījuma 3. nodaļa tika veikta praktiskā izpēte, kurā tiek analizēti novērojumi, izvērtēti bērnu lasītprasmes iemaņas, tiek izskatīti didaktiskas spēles un rotaļas veiksmīgai lasītprasmes veicināšanai. Kvalifikācijas darbs sastāv no 47. lappusēm, tsk. 4. tabulas, 3. diagrammas un 5. pielikumi. Pētījumā izmantoti 33. informācijas avots. Atslēga vārdi: lasītprasmes veicināšana, 5-6 gadīgie bērni, pirmsskola.The topic of the qualification work: “Promoting Reading Skills of 5-6 Years Old Children In The Preschool”. The objective of the study: to examine and analyze reading-promoting factors in 5-6 year old children. The study consists of 2 chapters and 10 sub-chapters. Chapter 1 deals with the general development of children aged 5-6, the development of reading skills, and the findings of educators and psychologists about that. Chapter 2 is devoted of the study to children's literacy processes. It examines the readiness of children to promote literacy, the researcher's thoughts on bilingualism, and readiness to readability. Chapter 3 of the study was a practical study, which analysed observations, assessed children's literacy skills, considered didactic games and games for successful reading literacy. The qualification paper consists of 47 pages, including 4 tables, 3 charts, and 5 appendices. There are 33 sources of information used in the study. Keywords: reading skills, 5-6 years, the preschool

    Simulation of the Optical Properties of Multilayer Structures Containing Layers of Porous Silicon and Optical Coatings

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    Моделируются оптические процессы отражения и пропускания в многослойной структуре, содержащей слои пористого кремния и оптические покрытия. Показано, что использование пористого кремния и пленок фторида диспрозия и сульфида цинка может значительно улучшить основные оптические характеристики светочувствительной структуры. Optical processes of reflection and transmission in a multilayer structure containing layers of porous silicon and optical coatings are modelled. It is shown that the use of porous silicon and films of dysprosium fluoride and zinc sulphide can significantly improve the basic optical characteristics of the photosensitive structure

    A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells

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    Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes

    The influence of technological parameters on the optical properties of photosensitive structures based on porous silicon

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    Мы изучаем фоточувствительные структуры, содержащие слои пористого кремния, изготовленные по различным технологическим маршрутам. Исследованы спектральные характеристики коэффициента отражения структур с пористым слоем и их фоточувствительность. Показано влияние диффузии на оптические свойства структур. We study photosensitive structures containing porous silicon layers made on different technological routes. The spectral characteristics of the reflection coefficient of structures with a porous layer and their photosensitivity are investigated. The effect of diffusion on the optical properties of structures
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