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Item Restricted Oral administration of chitosan/DNA nanoparticles containing DNA coding for FVIII and FC IgG fragment or IL-10 for the modulation of immune responses to FVIII in hemophilia mice(Nazarbayev University School of Science and Technology, 2016) Yerkesh, ZhadyraHemophilia A is an X-linked bleeding disorder, which occurs due to deficiency of clotting protein FVIII. Current treatment involves regular lifelong infusion of recombinant or plasma-derived FVIII protein, which is suboptimal, invasive and very expensive. One of the biggest challenges of the current therapy is the recognition of FVIII by immune system as a foreign substance, leading to the development of neutralizing antibodies, which makes further administration of FVIII ineffective. Therefore, an alternative cost effective and safe treatment to Hemophilia A is highly desirable. We propose chitosan-mediated oral non-viral gene therapy as a safe and costeffective strategy for immune modulation in severe hemophilia A cases. Having a strong affinity for DNA and forming nanoparticles, chitosan-DNA complexes protect plasmid DNA fi-om degradation by the low pH envu-onment of the stomach and from nucleases in the GI tract; further, safe re-administration of nanoparticles is possible. We also propose to include in the plasmid DNA coding for the Fc fragment of IgG heavy chain region, which contains Tregitope sequences, T cell epitopes that specifically activate regulatory T cells or anti-inflammatory cytokine IL-10 that may modulate the immune response against FVIII protein. Therefore, it is hypothesized that orally administered chitosan/DNA nanoparticles will lead to clinically relevant amount of FVIII in the host without an immune response, providing long term, cost-effective and safe treatment for hemophilia A. For this study we aimed to: I) optimize nanoparticles in terms of effective gene expression in vitro; 2) treat hemophilic mice orally with chitosan nanoparticles containing DNA coding for FVIII and for immunomodulatory elements (Fc fragment of IgG and IL-10) to induce tolerance to FVIII. We found that the key factors contributing to the effectiveness of gene expression in chitosan/DNA nanoparticles are the type of chitosan, the charge ratio (N/P) and the DNA concentration. In vivo, the optimized nanoparticles containing FVIII+Fc DNA significantly decreased antibody formation specific to F V I I I in prophylactic group of mice, and in 4/6 mice receiving nanoparticles containing FVIII+IL-10. It is tempting to hypothesize that this strategy might also be extended to modulate immune responses to other antigens.Item Restricted Migration characteristics of cancer cells grown in embryonic microenvironment and under antiviral agents(Nazarbayev University School of Science and Technology, 2016) Karapina, OrynbassarThis study describes a method for investigating reprogramming of cancer cells using chicken embryo extract and dimishing cancer cell progressing with acyclovir and it was used as innovative approach to address whether aggressive cancer cells with high potential to proliferate and migrate to distant organs could respond to the treatments, which could control cell fate determinationItem Restricted Development of flow cytometry and microscopy techniques to monitor freshwater phytoplankton communities in Kazakhstani lakes(Nazarbayev University School of Science and Technology, 2016) Dashkova, VeronikaIn this project, we tested an approach based on separating fluorescent viability and metabolic dyes between different excitation lasers in order to reach minimal spectral overlap with the autofluorescent signal using flow and imaging cytometryItem Restricted Co-expression of FVIII with human IGG FC Fragment or mouse IL-10 in encapsulated G8 myoblast cells as a potential treatment of hemophilia A(Nazarbayev University School of Science and Technology, 2016) Kanketayeva, ZhansayaIn this master thesis study we have shown that recombination G8 myoblasts, encapsulated in alginate-PLL microcapsules can successfully secrete detectable levels of both Fc and IL-10 out of the capsules and sustain good viability, showing the potential of co-delivering FVIII by encapsulated cells.Item Restricted Role of astrocyte aging in the pathogenesis of Alzheimer`s disease(Nazarbayev University School of Science and Technology, 2016) Imangali, NurgulIn this study we presented in vitro model for replicative senescence of primary human astrocytes isolated from fetal brainsItem Restricted Morphometric characteristics of cancer cells grown in embryonic microenvironment and under antiviral treatment(Nazarbayev University School of Science and Technology, 2016) Shaimerdenova, MadinaWe describe here that both embryonic microenvironment treatment and antiviral treatment have the potential to serve as effective factors in changing morphometric characteristics of two highly aggressive cancer cell lines, with proven capability to decrease viability of cancer cells, reduce amount of colonies formed after treatment, alter intracellular features of cell such as nucleus and cytoskeleton and diminish aldehyde dehydrogenase activity after treatmentItem Restricted Concentration dependent mitostatic effect and inhibition of cell motibility by different tubulin binding drugs-comparative study(Nazarbayev University School of Science and Technology, 2016) Balabiyev, ArnatHere, we demonstrate the comparative effects of nocodazole, taxol and vinorelbine on mitotic progression and cell motility using mouse fibroblasts and three cancer cell linesItem Restricted Application of advanced molecular techniques for analyzing phytoplankton population in Burabay National Nature Park Resort(Nazarbayev University School of Science and Technology, 2016) Sarsembekova, AsselIn this work, the molecular techniques as DNA extraction, DNA quantification, PCR analysis were optimized and subsequent sequencing was performed on MiSeq platform (Illumina, USA). We aimed to apply molecular methods to analyse phytoplankton population inhabiting Lake Shortan and Lake Burabay