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Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.

In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced pulmonary inflammatory response in rats exposed repeatedly for 14 days (12.5, 25, and 50 ��g/time, total six times). In this study, we tried to clarify the causes of different responses induced by both SiNPs using mice (12.5, 25, and 50 ��g/lung) and mouse alveolar macrophage cells. When exposed to alveolar macrophage cells for 24 h, both SiNPs decreased cell viability and enhanced ROS generation compared to controls. The 20- and 50-SiNPs also formed giant and autophagosome-like vacuoles in the cytoplasm, respectively. Structural damage of organelles was more pronounced in 20-SiNPs-treated cells than in 50-SiNPs-treated cells, and an increased mitochondrial membrane potential and mitochondrial calcium accumulation were observed only in the 20-SiNPs-treated cells. Additionally, a single intratracheal instillation of both sizes of SiNPs to mice clearly elevated the relative proportion of neutrophils and inhibited differentiation of macrophages and expression of an adhesion molecule. Meanwhile, interestingly, the total number of pulmonary cells and the levels of pro-inflammatory mediators more notably increased in the lungs of mice exposed to 20-SiNPs compared to 50-SiNPs. Given that accumulation of giant vacuoles and dilation of the ER and mitochondria are key indicators of paraptosis, we suggest that 20-SiNPs-induced pulmonary inflammation may be associated with paraptosis of alveolar macrophages.

The purpose of this thesis is to present a test case for diachronic and synchronic approaches in the book of Joshua, especially Josh 3-4 which is one of the most complex texts in the Old Testament. The thesis pays attention to how Polzin's approach, which is regarded one of the best sympathetic readings of Joshua, is applied to the text of Josh 3-4, and the relevance of the theories of Auld. After preliminaries in Chapter One, Chapter Two introduces the synchronic readings of Polzin, Hawk, Mitchell, and Winther-Nielsen, attempts to uncover the problems in applying their methods to this complicated text, and offers a critique of these sympathetic readings. Through this examination, the writer concludes that Polzin's methodology does explain a number of difficult problems in this text, but also that his reading has limitations. One important question is the relevance of these several approaches to the two different descriptions concerning the twelve stones set up in the middle ofthe Jordan and on the other side of the river. Chapter Three investigates the differences between the MT and the LXX of Joshua 3-4 through text critical analysis, reconstructs the Hebrew Vorlage of LXXJoshua 3-4 considering divergences between major Greek editions (Margolis, Rahlfs, and Auld), and examines the limitations of Polzin's synchronic study in reading only from the final text of MT. The large number of text critical issues in this text (Josh 3- 4) makes it difficult to work only from the final form of the MT. A further difficulty is deciding which text we should follow among the MT, LXX, and Vorlage behind the Greek text. The impossibility of simple answers drives us to sympathize with a diachronic approach. For the purpose of reading the literary history of Josh 3-4 in a diachronic way, the writer considers what position this text holds in the setting of the wider context of the ark narratives and water-crossing stories in the Old Testament. Thus, Chapter Four compares the ark story in this text with those in the Pentateuch and other Former Prophets. Chapter Five compares Joshua 3-4 with the crossing of the Reed Sea in Exodus 13:17-14:31 and with Elijah and Elisha crossing the river in 2 Kings 2. In these two chapters, the writer considers recent trends in literary criticism which reject the existence of a Yahwist (J) and prefer to call material which does not belong to P simply 'non-Priestly', and suggests new directions for literary criticism. One of these specific features is to read the Pentateuch and the Former Prophets in reverse order. In this part, the writer examines the relevance of Auld's theory, in which the shared material by Samuel-Kings and Chronicles is the root work of the story of Israel before the monarchy With the help of the investigations already mentioned, Chapter Six attempts to read the literary history of Joshua 3-4 based on the Hebrew Vorlage of LXX and on MT of Josh 3-4. This chapter retraces the complex literary history of Josh 3-4 and discusses the limitations of Polzin's synchronic study in reading Josh 3-4 only from the final text of MT.