Chromatin remodeling protein Smarca5 participates on many cellular processes, which are important for tissue development and tumorigenesis. Among these processes utilizing ATPase activity of Smarca5 belong also transcription, replication and DNA repair. We hypothesized that Smarca5 represents essential molecule for chromatin modulation primarily at early developmental stages at the level of fast-dividing progenitors of many origins, in whose the ATPase is highly expressed. To such tissues may belong also hematopoiesis, in which the Smarca5 has highest expression. The subject of my doctoral thesis is therefore analysis of the effect Smarca5 depletion on proliferation and differentiation of hematopoietic progenitors in vivo and a search for mechanisms behind the resulted developmental defects. We utilized conditionally knockout allele of Smarca5 in blood precursors to study in a mouse model how depletion of the ISWI ATPase causes accumulation of earliest progenitors inhibited from further maturation to erythroid and other myeloid lines. The proerythroblasts became dysplastic and the majority of basophilic erythroblasts ceased cycling around the G2/M stage. An expected mechanism for observed changes appeared the activation of stress pathway of protein p53 that is often associated with unrepaired DNA...

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During the last decade governments and international organizations have taken multipleactions to combat money laundering. Despite this, anti-money laundering policies have haddubious effects. This paper investigates efforts to combat money laundering from theFoucauldian ideas of governmentality. By investigating Sweden’s efforts to fight moneylaundering the paper sheds light on the different problematizations, rationalities, identityformations, techniques, and mechanisms that can be found in Sweden’s anti-moneylaundering regime. By focusing on the Swedish Financial Supervisory Authority, the CountyAdministrative Board and private actors this paper provides insights into how the regimegoverns through knowledge-based technologies of government and risk-based rationality.

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In the field of cancer immunotherapy, NK cells are recognized for their ability to provide a form of innate immunity against tumor cells. However, the average abundance of NK cells in the blood can be as low as 5% of the total lymphocyte population. As a result, it has been a focus to find novel therapies to expand NK cells in vitro while subsequently enhancing the cytotoxicity of these cells. Previously-defined methods include the minimal expansion of NK cells with high levels of cytokines such as IL-2 and IL-15, as well as co-culturing NK cells with feeder cell populations that are genetically modified to express NK-stimulating factors. Another method involves the use of artificially-derived plasma membrane nanoparticles (PM21) that express membrane-bound IL-21 (mb21) to successfully expand NK cells by a factor of 103 in 14 days. Exosomes, which are cell-derived vesicles naturally secreted by cancer cells, may reveal a novel way to expand NK cells and enhance their cytotoxicity by taking advantage of the exchange of genetic information within the tumor microenvironment. To test this hypothesis, NK cells have been cultured with varying concentrations of exosomes derived from modified K562-mb21-41BBl (a chronic myelogenous leukemia cell line) and shown to achieve 200-fold expansion of NK cells from other PBMCs in 14 days, a growth comparable to that of PM-21 particles. In vitro assays as well as co-culturing with various tumor cell lines will determine the cytotoxicity of these expanded cells. Potentially, exosomes may be applied as an in vivo therapy for NK cell expansion.

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